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|Coordinate||71,334,101 bp (GRCm38)|
|Base Change||A ⇒ G (forward strand)|
|Gene Name||CD8 antigen, beta chain 1|
|Synonym(s)||Ly-3, Ly-C, Lyt-3|
|Chromosomal Location||71,322,812-71,337,451 bp (+)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 antigen, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigens displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. This gene encodes the CD8 beta chain isoforms. Multiple alternatively spliced transcript variants encoding distinct membrane associated or secreted isoforms have been described. A pseudogene, also located on chromosome 2, has been identified. [provided by RefSeq, May 2010]
PHENOTYPE: Animals homozygous for a mutation in this gene lack CD8+CD4- cytotoxic T cells in the thymus and spleen and do not mount a cytotoxic response to alloantigens. [provided by MGI curators]
|Amino Acid Change||Arginine changed to Glycine|
|Institutional Source||Beutler Lab|
|Gene Model||predicted gene model for protein(s): [ENSMUSP00000070131]|
AA Change: R202G
|Predicted Effect||probably damaging
PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
|Phenotypic Category||Autosomal Semidominant|
|Alleles Listed at MGI|
|Mode of Inheritance||Autosomal Semidominant|
|Last Updated||2016-12-30 2:41 PM by Katherine Timer|
|Record Created||2015-12-21 11:51 AM|
The Carlsbad phenotype was identified among G3 mice of the pedigree R2860, some of which showed an increase in the CD4+ to CD8+ T cell ratio (Figure 1) caused by a diminished frequency of CD8+ T cells in CD3+ T cells (Figure 2) coupled with an increase in the frequency of CD4+ T cells in CD3+ T cells (Figure 3), all in the peripheral blood. Also, the T-dependent antibody response to recombinant Semliki Forest virus (rSFV)-encoded β-galactosidase (rSFV-β-gal) was increased in the Carlsbad mice (Figure 4).
|Nature of Mutation|
Whole exome HiSeq sequencing of the G1 grandsire identified 45 mutations. All of the above anomalies were linked by continuous variable mapping to a mutation in Cd8b1: an A to G transition at base pair 71,334,101 (v38) on chromosome 6, or base pair 11,290 in the GenBank genomic region NC_000072 encoding Cd8b1. The strongest association was found with an additive model of linkage to the normalized CD4:CD8 ratio, wherein four variant homozygotes and 15 heterozygotes departed phenotypically from five homozygous reference mice with a P value of 1.124 x 10-5 (Figure 5).
The mutation corresponds to residue 649 in the mRNA sequence NM_009858 within exon 5 of 6 total exons.
The mutated nucleotide is indicated in red. The mutation results in an arginine (R) to glycine (G) substitution at position 202 (R202G) in the CD8β protein, and is strongly predicted by PolyPhen-2 to be damaging (score = 0.996) (1).
CD8β (also known as Lyt-3) is a 213-amino acid single pass type I transmembrane glycoprotein of the immunoglobulin (Ig) superfamily (Figure 6) (2). CD8β heterodimerizes with CD8α (also known as Lyt-2; see the record for alfalfa) to form CD8αβ, which functions as a coreceptor for the T cell receptor (TCR) [reviewed in (3)]. CD8β requires an association with CD8α to translocate to the cell surface; unassociated CD8β is retained in the endoplasmic reticulum and degraded (4-6). Human CD8β, but not mouse CD8β, can form a CD8ββ homodimer (7). The lack of CD8ββ homodimers in the mouse is attributed to the Ig domain found in mouse, but not human, CD8β. The CD8ββ could not bind MHC class I.
The extracellular domain of CD8β increases the avidity of CD8 binding to MHC I (8). The intracellular domain of CD8β promotes the association with Lck and LAT, two proteins required for TCR signal transduction, as well as (9). The intracellular and extracellular domains of CD8β can both independently promote CD8+ T cell development, but both domains together is most efficient (8;9).
Connecting the Ig-like domain to the transmembrane domain is the stalk region of CD8β. The stalk region of CD8β is essential for selection of CD8+ class I MHC-restricted T cells as well as the response of peripheral T cells; the stalk region is not required for expression of CD8β on the cell surface (10). The stalk region enhances the coreceptor function of CD8, making the CD8αβ heterodimer a better coreceptor than CD8αα (11). The stalk region is heavily O-glycosylated. O-glycosylation of CD8β is developmentally regulated such that immature double positive thymocytes display lower levels than mature thymocytes (12-15). This relative difference influences thymocyte selection in that decreased levels of CD8β O-glycosylation in immature thymocytes correlate with increased affinity for pMHC I; the enhanced CD8-pMHCI binding promotes elimination of autoreactive T cells in the thymus (12;15). In contrast, higher levels of O-glycosylation in mature T cells reduce CD8 affinity for pMHCI, thereby requiring stronger TCR-pMHCI binding for T cell activation. The structural mechanism by which O-glycosylation alters CD8 affinity for pMHCI is unknown (16); in published 3D crystal structures the stalk region has been disordered. O-glycosylation has been reported to increase the rigidity of polypeptides, as observed in mucins, and may limit the mobility of the Ig-like domains of CD8αα and CD8αβ [reviewed in (3)]. O-glycosylation of CD8α does not appear to be developmentally regulated (14).
CD8α and CD8β share approximately 20% homology within the Ig domains. The crystal structure of the Ig-like domains of mouse CD8αβ [Figure 7; PDB:2ATP; (17)] resembles the variable domain fragment (Fv) of an antibody, with each chain adopting a V-set type Ig fold (17;18); this structure is similar to that of the Ig-like domains in the CD8αα dimer (19;20). The two chains of both dimers have similar conformations, including a disulfide bond between the B and F β-strands, and a tryptophan on the C strand.
Palmitoylation of CD8β promotes the segregation of CD8 into lipid rafts, a critical step in facilitating the function of CD8 as a coreceptor with the TCR (21). Furthermore, CD8β directly associates with CD3δ to facilitate the trafficking of the TCR into lipid rafts (22).
Either CD4 (see thoth) or CD8 and the TCR (αβ unless otherwise indicated) mediate T cell recognition of antigen-MHC complexes on the surface of antigen presenting cells. Expression of CD4 versus CD8αβ by a given T cell restricts TCR recognition of peptides to those bound to either MHCII or MHCI, respectively. CD4 and CD8αβ contact a conserved membrane-proximal region of their MHC target to enforce MHC class restriction. The molecular details of the interaction between CD8αβ with the peptide-MHCI complex (pMHCI) have been investigated by X-ray crystallography (18;20;23). The 3D structures revealed that the extracellular Ig-like domain of both the CD8αβ and the CD8αα dimers contact the α3 domain of the MHC I heavy chain, whereas CD8αα additionally contacts the α2 domain and β2-microglobulin. Three complementarity-determining regions (CDRs), consisting of the BC loop (CDR1), the C’C” loop (CDR2), and the FG loop (CDR3), are involved in binding to the α3 domain of pMHCI. Residues in the CDR1 (Lys23), CDR2 (Lys55), and CDR3 (Val99, Ser101, and Lys103) loops of CD8β decreased MHC I binding and T cell activation (24). The CD8β subunit of CD8αβ is positioned next to the T cell membrane, while the CD8α subunit is distal from the T cell and close to the C-terminus of the MHCI α3 domain. Differences exist between the CD8αα/pMHCI interface and the CD8αβ/pMHCI interface despite the fact that overall conformations are quite similar. Importantly, nearly all MHCI residues making key contacts with CD8αα and CD8αβ are non-polymorphic; thus CD8αα and CD8αβ bind to different MHCI alleles with only subtly different affinities (25;26). However, reports suggest that CD8αβ is a more effective coreceptor than CD8αα in enhancing the range and sensitivity to peptide antigens and alloantigens recognized by TCRs (27-30). The stalk or intracellular region of CD8β may facilitate a configuration that promotes this augmented function (30-33).
Human CD8B has several alternatively spliced variants that encode differerent cytoplasmic tails (M-1, M-2, M-3, M-4); mouse Cd8b1 does not encode multiple transcripts (34). In total CD8+ T cells, the expression level of the M-1 vairant was the highest and the M-3 variant was the lowest. The M-4 isoform was the highest expressed variant in effector memory CD8+ T cells. After CD8+ T cell stimulation, the expression level of the M-2 variant increased 10 to 20 fold relative to resting cells in contrast to the other isoforms.
The mutation results in an arginine (R) to glycine (G) substitution at position 202 (R202G); residue 202 is within the cytoplasmic domain.
T cells become activated when the TCR engages a peptide antigen in complex with an MHC molecule on the surface of a target or antigen-presenting cell. However, TCR-pMHC interaction is not by itself sufficient to induce an effective T cell response. Rather, engagement of pMHC by the TCR and either the CD4 or CD8 coreceptor is necessary for optimal T cell stimulation (39;40). For cytotoxic T cells, the interaction of CD8 with MCHI enhances the antigen sensitivity and response of the T cells to pMHC ligands (41). CD8 contacts invariant sites on the membrane-proximal region of the MHCI molecule in the context of the composite pMHCI complex. These sites are distinct and physically distant from the sites bound by the TCR, permitting both coreceptor and TCR to bind the same pMHCI complex (20). Absent CD8-pMHCI interaction, MHC class I-restricted immune responses including cytokine production and cytotoxic effector function are impaired (39;40). However, high-affinity pMHC/TCR interactions can in some cases compensate for a lack of CD8 engagement in terms of Lck activation, T cell proliferation, and cytotoxic T lymphocyte (CTL) activity (42). Discussed here is the TCR coreceptor function of the CD8αβ heterodimer.
For an in-depth discussion on the function of the CD8αβ heterodimer, please see the record for alfalfa.
Rather than physically promoting initial TCR-pMHCI binding, the major function of CD8αβ is to recruit the kinase Lck to the TCR-MHC interaction site where it can phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the cytoplasmic tails of associated CD3 proteins (see tumormouse, a mutation of Cd3e, and allia, a mutation of Cd247) (43;44). Their phosphorylation recruits and activates other proteins including ZAP-70 (ζ-chain-associated protein of 70 kDa; see murdock), SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa), and LAT (linker for activation of T cells) necessary for signaling leading to T cell activation, proliferation, and differentiation (Figure 8; also see iconoclast for a description of TCR signaling). The CD8-pMHCI interaction synergistically stabilizes TCR-pMHCI interactions (45). However, it has also been reported that CD8αβ can play a critical role in promoting TCR-pMHCI binding, particularly for multimeric low-affinity pMHCI ligands (46;47).
TCR signaling is necessary for both adaptive immune responses and for thymocyte differentiation (Figure 9). CD8αβ is required for both positive and negative selection of double positive cells in the thymus (48-50). Cd8b1-deficient mice exhibited a five-fold reduction in the numbers of CD8+ T cells in the thymus and the periphery; the CD8+ T cells that remained had normal cytotoxic T lymphocyte activity (48-51). CD8α expression on thymocytes and peripheral T cells was reduced compared to that in wild-type mice (51). The population size and CD8α expression was normal in intraepithelial lymphocytes from the Cd8b1-deficient mice due to the predominant expression of CD8αα homodimers on these cells (51). Peripheral T cells from the Cd8b1-deficient mice did not exhibit defective cytotoxic activity against lymphocytic choriomeningitis virus or vesicular stomatitis virus (51-53). The phenotype of the Carlsbad mice indicates loss of CD8β function.
Carlsbad(F):5'- AGTTTCCACCCACGTGAGATG -3'
Carlsbad(R):5'- TGAGGATGACTGGGAACTTCC -3'
Carlsbad_seq(F):5'- GCTATTAGAATCATGGAATGGATGAC -3'
Carlsbad_seq(R):5'- GTCCTGGAACTCACTATGTAGAC -3'
1. Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., and Sunyaev, S. R. (2010) A Method and Server for Predicting Damaging Missense Mutations. Nat Methods. 7, 248-249.
2. Nakauchi, H., Shinkai, Y., and Okumura, K. (1987) Molecular Cloning of Lyt-3, a Membrane Glycoprotein Marking a Subset of Mouse T Lymphocytes: Molecular Homology to Immunoglobulin and T-Cell Receptor Variable and Joining Regions. Proc Natl Acad Sci U S A. 84, 4210-4214.
3. Li, Y., Yin, Y., and Mariuzza, R. A. (2013) Structural and Biophysical Insights into the Role of CD4 and CD8 in T Cell Activation. Front Immunol. 4, 206.
4. Norment, A. M., and Littman, D. R. (1988) A Second Subunit of CD8 is Expressed in Human T Cells. EMBO J. 7, 3433-3439.
5. Gorman, S. D., Sun, Y. H., Zamoyska, R., and Parnes, J. R. (1988) Molecular Linkage of the Ly-3 and Ly-2 Genes. Requirement of Ly-2 for Ly-3 Surface Expression. J Immunol. 140, 3646-3653.
6. Bosselut, R., Zhang, W., Ashe, J. M., Kopacz, J. L., Samelson, L. E., and Singer, A. (1999) Association of the Adaptor Molecule LAT with CD4 and CD8 Coreceptors Identifies a New Coreceptor Function in T Cell Receptor Signal Transduction. J Exp Med. 190, 1517-1526.
7. Devine, L., Kieffer, L. J., Aitken, V., and Kavathas, P. B. (2000) Human CD8 Beta, but Not Mouse CD8 Beta, can be Expressed in the Absence of CD8 Alpha as a Beta Beta Homodimer. J Immunol. 164, 833-838.
8. Bosselut, R., Kubo, S., Guinter, T., Kopacz, J. L., Altman, J. D., Feigenbaum, L., and Singer, A. (2000) Role of CD8beta Domains in CD8 Coreceptor Function: Importance for MHC I Binding, Signaling, and Positive Selection of CD8+ T Cells in the Thymus. Immunity. 12, 409-418.
9. Irie, H. Y., Mong, M. S., Itano, A., Crooks, M. E., Littman, D. R., Burakoff, S. J., and Robey, E. (1998) The Cytoplasmic Domain of CD8 Beta Regulates Lck Kinase Activation and CD8 T Cell Development. J Immunol. 161, 183-191.
10. Rettig, L., McNeill, L., Sarner, N., Guillaume, P., Luescher, I., Tolaini, M., Kioussis, D., and Zamoyska, R. (2009) An Essential Role for the Stalk Region of CD8 Beta in the Coreceptor Function of CD8. J Immunol. 182, 121-129.
11. Wong, J. S., Wang, X., Witte, T., Nie, L., Carvou, N., Kern, P., and Chang, H. C. (2003) Stalk Region of Beta-Chain Enhances the Coreceptor Function of CD8. J Immunol. 171, 867-874.
12. Moody, A. M., North, S. J., Reinhold, B., Van Dyken, S. J., Rogers, M. E., Panico, M., Dell, A., Morris, H. R., Marth, J. D., and Reinherz, E. L. (2003) Sialic Acid Capping of CD8beta Core 1-O-Glycans Controls Thymocyte-Major Histocompatibility Complex Class I Interaction. J Biol Chem. 278, 7240-7246.
13. Wu, W., Harley, P. H., Punt, J. A., Sharrow, S. O., and Kearse, K. P. (1996) Identification of CD8 as a Peanut Agglutinin (PNA) Receptor Molecule on Immature Thymocytes. J Exp Med. 184, 759-764.
14. Casabo, L. G., Mamalaki, C., Kioussis, D., and Zamoyska, R. (1994) T Cell Activation Results in Physical Modification of the Mouse CD8 Beta Chain. J Immunol. 152, 397-404.
15. Daniels, M. A., Devine, L., Miller, J. D., Moser, J. M., Lukacher, A. E., Altman, J. D., Kavathas, P., Hogquist, K. A., and Jameson, S. C. (2001) CD8 Binding to MHC Class I Molecules is Influenced by T Cell Maturation and Glycosylation. Immunity. 15, 1051-1061.
16. Merry, A. H., Gilbert, R. J., Shore, D. A., Royle, L., Miroshnychenko, O., Vuong, M., Wormald, M. R., Harvey, D. J., Dwek, R. A., Classon, B. J., Rudd, P. M., and Davis, S. J. (2003) O-Glycan Sialylation and the Structure of the Stalk-Like Region of the T Cell Co-Receptor CD8. J Biol Chem. 278, 27119-27128.
17. Chang, H. C., Tan, K., Ouyang, J., Parisini, E., Liu, J. H., Le, Y., Wang, X., Reinherz, E. L., and Wang, J. H. (2005) Structural and Mutational Analyses of a CD8alphabeta Heterodimer and Comparison with the CD8alphaalpha Homodimer. Immunity. 23, 661-671.
18. Wang, R., Natarajan, K., and Margulies, D. H. (2009) Structural Basis of the CD8 Alpha beta/MHC Class I Interaction: Focused Recognition Orients CD8 Beta to a T Cell Proximal Position. J Immunol. 183, 2554-2564.
19. Kern, P. S., Teng, M. K., Smolyar, A., Liu, J. H., Liu, J., Hussey, R. E., Spoerl, R., Chang, H. C., Reinherz, E. L., and Wang, J. H. (1998) Structural Basis of CD8 Coreceptor Function Revealed by Crystallographic Analysis of a Murine CD8alphaalpha Ectodomain Fragment in Complex with H-2Kb. Immunity. 9, 519-530.
20. Gao, G. F., Tormo, J., Gerth, U. C., Wyer, J. R., McMichael, A. J., Stuart, D. I., Bell, J. I., Jones, E. Y., and Jakobsen, B. K. (1997) Crystal Structure of the Complex between Human CD8alpha(Alpha) and HLA-A2. Nature. 387, 630-634.
21. Arcaro, A., Gregoire, C., Bakker, T. R., Baldi, L., Jordan, M., Goffin, L., Boucheron, N., Wurm, F., van der Merwe, P. A., Malissen, B., and Luescher, I. F. (2001) CD8beta Endows CD8 with Efficient Coreceptor Function by Coupling T Cell receptor/CD3 to Raft-Associated CD8/p56(Lck) Complexes. J Exp Med. 194, 1485-1495.
22. Doucey, M. A., Goffin, L., Naeher, D., Michielin, O., Baumgartner, P., Guillaume, P., Palmer, E., and Luescher, I. F. (2003) CD3 Delta Establishes a Functional Link between the T Cell Receptor and CD8. J Biol Chem. 278, 3257-3264.
23. Shi, Y., Qi, J., Iwamoto, A., and Gao, G. F. (2011) Plasticity of Human CD8alphaalpha Binding to Peptide-HLA-A*2402. Mol Immunol. 48, 2198-2202.
24. Devine, L., Thakral, D., Nag, S., Dobbins, J., Hodsdon, M. E., and Kavathas, P. B. (2006) Mapping the Binding Site on CD8 Beta for MHC Class I Reveals Mutants with Enhanced Binding. J Immunol. 177, 3930-3938.
25. Garcia, K. C., Scott, C. A., Brunmark, A., Carbone, F. R., Peterson, P. A., Wilson, I. A., and Teyton, L. (1996) CD8 Enhances Formation of Stable T-Cell receptor/MHC Class I Molecule Complexes. Nature. 384, 577-581.
26. Gao, G. F., Willcox, B. E., Wyer, J. R., Boulter, J. M., O'Callaghan, C. A., Maenaka, K., Stuart, D. I., Jones, E. Y., Van Der Merwe, P. A., Bell, J. I., and Jakobsen, B. K. (2000) Classical and Nonclassical Class I Major Histocompatibility Complex Molecules Exhibit Subtle Conformational Differences that Affect Binding to CD8alphaalpha. J Biol Chem. 275, 15232-15238.
27. Wheeler, C. J., von Hoegen, P., and Parnes, J. R. (1992) An Immunological Role for the CD8 Beta-Chain. Nature. 357, 247-249.
28. Karaki, S., Tanabe, M., Nakauchi, H., and Takiguchi, M. (1992) Beta-Chain Broadens Range of CD8 Recognition for MHC Class I Molecule. J Immunol. 149, 1613-1618.
29. Renard, V., Romero, P., Vivier, E., Malissen, B., and Luescher, I. F. (1996) CD8 Beta Increases CD8 Coreceptor Function and Participation in TCR-Ligand Binding. J Exp Med. 184, 2439-2444.
30. Witte, T., Spoerl, R., and Chang, H. C. (1999) The CD8beta Ectodomain Contributes to the Augmented Coreceptor Function of CD8alphabeta Heterodimers Relative to CD8alphaalpha Homodimers. Cell Immunol. 191, 90-96.
31. Kern, P., Hussey, R. E., Spoerl, R., Reinherz, E. L., and Chang, H. C. (1999) Expression, Purification, and Functional Analysis of Murine Ectodomain Fragments of CD8alphaalpha and CD8alphabeta Dimers. J Biol Chem. 274, 27237-27243.
32. Wong, J. S., Wang, X., Witte, T., Nie, L., Carvou, N., Kern, P., and Chang, H. C. (2003) Stalk Region of Beta-Chain Enhances the Coreceptor Function of CD8. J Immunol. 171, 867-874.
33. Rettig, L., McNeill, L., Sarner, N., Guillaume, P., Luescher, I., Tolaini, M., Kioussis, D., and Zamoyska, R. (2009) An Essential Role for the Stalk Region of CD8 Beta in the Coreceptor Function of CD8. J Immunol. 182, 121-129.
34. Thakral, D., Dobbins, J., Devine, L., and Kavathas, P. B. (2008) Differential Expression of the Human CD8beta Splice Variants and Regulation of the M-2 Isoform by Ubiquitination. J Immunol. 180, 7431-7442.
35. Terry, L. A., DiSanto, J. P., Small, T. N., and Flomenberg, N. (1990) Differential Expression and Regulation of the Human CD8 Alpha and CD8 Beta Chains. Tissue Antigens. 35, 82-91.
36. Moebius, U., Kober, G., Griscelli, A. L., Hercend, T., and Meuer, S. C. (1991) Expression of Different CD8 Isoforms on Distinct Human Lymphocyte Subpopulations. Eur J Immunol. 21, 1793-1800.
37. Mayans, S., Stepniak, D., Palida, S. F., Larange, A., Dreux, J., Arlian, B. M., Shinnakasu, R., Kronenberg, M., Cheroutre, H., and Lambolez, F. (2014) AlphabetaT Cell Receptors Expressed by CD4(-)CD8alphabeta(-) Intraepithelial T Cells Drive their Fate into a Unique Lineage with Unusual MHC Reactivities. Immunity. 41, 207-218.
38. DiSanto, J. P., Knowles, R. W., and Flomenberg, N. (1988) The Human Lyt-3 Molecule Requires CD8 for Cell Surface Expression. EMBO J. 7, 3465-3470.
39. Connolly, J. M., Hansen, T. H., Ingold, A. L., and Potter, T. A. (1990) Recognition by CD8 on Cytotoxic T Lymphocytes is Ablated by several Substitutions in the Class I Alpha 3 Domain: CD8 and the T-Cell Receptor Recognize the Same Class I Molecule. Proc Natl Acad Sci U S A. 87, 2137-2141.
40. Salter, R. D., Benjamin, R. J., Wesley, P. K., Buxton, S. E., Garrett, T. P., Clayberger, C., Krensky, A. M., Norment, A. M., Littman, D. R., and Parham, P. (1990) A Binding Site for the T-Cell Co-Receptor CD8 on the Alpha 3 Domain of HLA-A2. Nature. 345, 41-46.
41. Holler, P. D., and Kranz, D. M. (2003) Quantitative Analysis of the Contribution of TCR/pepMHC Affinity and CD8 to T Cell Activation. Immunity. 18, 255-264.
42. Kerry, S. E., Buslepp, J., Cramer, L. A., Maile, R., Hensley, L. L., Nielsen, A. I., Kavathas, P., Vilen, B. J., Collins, E. J., and Frelinger, J. A. (2003) Interplay between TCR Affinity and Necessity of Coreceptor Ligation: High-Affinity Peptide-MHC/TCR Interaction Overcomes Lack of CD8 Engagement. J Immunol. 171, 4493-4503.
43. Artyomov, M. N., Lis, M., Devadas, S., Davis, M. M., and Chakraborty, A. K. (2010) CD4 and CD8 Binding to MHC Molecules Primarily Acts to Enhance Lck Delivery. Proc Natl Acad Sci U S A. 107, 16916-16921.
44. Purbhoo, M. A., Boulter, J. M., Price, D. A., Vuidepot, A. L., Hourigan, C. S., Dunbar, P. R., Olson, K., Dawson, S. J., Phillips, R. E., Jakobsen, B. K., Bell, J. I., and Sewell, A. K. (2001) The Human CD8 Coreceptor Effects Cytotoxic T Cell Activation and Antigen Sensitivity Primarily by Mediating Complete Phosphorylation of the T Cell Receptor Zeta Chain. J Biol Chem. 276, 32786-32792.
45. Jiang, N., Huang, J., Edwards, L. J., Liu, B., Zhang, Y., Beal, C. D., Evavold, B. D., and Zhu, C. (2011) Two-Stage Cooperative T Cell Receptor-Peptide Major Histocompatibility Complex-CD8 Trimolecular Interactions Amplify Antigen Discrimination. Immunity. 34, 13-23.
46. Daniels, M. A., and Jameson, S. C. (2000) Critical Role for CD8 in T Cell Receptor Binding and Activation by peptide/major Histocompatibility Complex Multimers. J Exp Med. 191, 335-346.
47. Denkberg, G., Cohen, C. J., and Reiter, Y. (2001) Critical Role for CD8 in Binding of MHC Tetramers to TCR: CD8 Antibodies Block Specific Binding of Human Tumor-Specific MHC-Peptide Tetramers to TCR. J Immunol. 167, 270-276.
48. Fung-Leung, W. P., Schilham, M. W., Rahemtulla, A., Kundig, T. M., Vollenweider, M., Potter, J., van Ewijk, W., and Mak, T. W. (1991) CD8 is Needed for Development of Cytotoxic T Cells but Not Helper T Cells. Cell. 65, 443-449.
49. Crooks, M. E., and Littman, D. R. (1994) Disruption of T Lymphocyte Positive and Negative Selection in Mice Lacking the CD8 Beta Chain. Immunity. 1, 277-285.
50. Nakayama, K., Nakayama, K., Negishi, I., Kuida, K., Louie, M. C., Kanagawa, O., Nakauchi, H., and Loh, D. Y. (1994) Requirement for CD8 Beta Chain in Positive Selection of CD8-Lineage T Cells. Science. 263, 1131-1133.
51. Fung-Leung, W. P., Kundig, T. M., Ngo, K., Panakos, J., De Sousa-Hitzler, J., Wang, E., Ohashi, P. S., Mak, T. W., and Lau, C. Y. (1994) Reduced Thymic Maturation but Normal Effector Function of CD8+ T Cells in CD8 Beta Gene-Targeted Mice. J Exp Med. 180, 959-967.
52. Angelov, G. S., Guillaume, P., and Luescher, I. F. (2009) CD8beta Knockout Mice Mount Normal Anti-Viral CD8+ T Cell Responses--but Why? Int Immunol. 21, 123-135.
|Science Writers||Anne Murray|
|Authors||Ming Zeng, Xue Zhong, and Bruce Beutler|
|List |< first << previous [record 56 of 511] next >> last >||