Cell-cell adhesion mediated by CD8 and MHC class I molecules

Norment, Anne M.; Salter, Russell D.; Parham, Peter; Engelhard, Víctor H.; Littman, Dan R.

doi:10.1038/336079a0

Cited by 405 publications

(208 citation statements)

References 34 publications

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“…MHC class I molecules present mainly endogenously derived antigenic peptides and stimulate primarily CD8 T cytotoxic cells [41]. Exogenously derived peptides are preferably presented by MHC class II molecules and stimulate mainly CD4 T helper (Th) cells [42].…”

Section: Discussionmentioning

confidence: 99%

Idiotype-induced T cell stimulation requires antigen presentation in association with HLA-DR molecules

Qu¹,

Holm²,

Lefvert³

1996

Clinical and Experimental Immunology

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SUMMARYAn important and yet unresolved question concerns the mode of T cell recognition of idiotypic epitopes on immunoglobulin molecules in humans. Results from murine and human studies show that some idiotype-specific T cells recognize conformational epitopes on immunoglobulin, and such T cells are not MHC-restricted. In the present study T cell stimulation induced by idiotypic determinants on the autologous monoclonal IgG (M-components) from patients with monoclonal gammopathies was studied. In parallel, T cell stimulation in response to a conventional antigen, purified protein derivative, was also examined. It is shown that, as with conventional antigen, idiotype-induced T cell stimulation requires the presence of antigen-presenting cells (APC; monocytes and/or B cells), and is MHC class II (DR)-restricted. B cells, but not monocytes, can present idiotypic determinants to T cells at very low antigen concentrations, while monocytes do so only when antigen is present at high concentrations. Antigen processing and presentation is abrogated by treatment of APC with chloroquine. In conclusion, our study demonstrates that human idiotype-specific T cells recognize processed idiotypic determinants presented by MHC class II (HLA-DR) molecules on APC, and that B cells require about 1000-fold less antigen than monocytes.

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Section: Discussionmentioning

confidence: 99%

Idiotype-induced T cell stimulation requires antigen presentation in association with HLA-DR molecules

Qu¹,

Holm²,

Lefvert³

1996

Clinical and Experimental Immunology

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“…Direct binding of CD8 to HLA class I and CD4 to HLA class II was shown using cell-cell adhesion assays in which CD8 or CD4 were expressed at high levels on the surface ofchinese hamster ovary (CHO) cells for CD8 (14) or monkey CV1 or COS 1 cells for CD4 (15,16) . Purified class I and CD8 molecules expressed in lipid-sealed spherical nylon vesicles also showed specific binding (17).…”

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confidence: 99%

Mutations in CD8 that affect interactions with HLA class I and monoclonal anti-CD8 antibodies.

Sanders

Fox

Kavathas

1991

The Journal of Experimental Medicine

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SummaryThe T cell co-receptor, CD8, binds to the 0 domain of HLA class I (Salter, R .D., R .J. Benjamin, P.K . Wesley, S .E. Buxton, T.P.J . Garrett, C. Clayberger, A.M . Krensky, A .M . Norman, D.R. Littman, and P Parham . 1990. Nature (Lond]. 345 :41; Connolly, J.M ., TA. Potter, E.M. Wormstall, and TH . Hansen. 1988 . J. ExpL Med. 168 :325 ; and Potter, TA., TV. Rajan, R.F. Dick II, and J .A . Bluestone . 1989 . Natur e (Lond.j. 337 :73). To identify regions of CD8 that are important for binding to HLA class I, we performed a mutational analysis of the CD8 molecule in the immunoglobulin (1g)-like variable domain. Our mutational analysis was based on our finding that using a cell-cell adhesion assay murine CD8 (Lyt-2) did not bind to human class I . Since the interaction of human CD8 with HLA class I is species specific, we substituted nonconservative amino acids from mouse CD8 and analyzed the ability of the mutated CD8 molecules expressed in COS 7 cells to bind HLA class I-bearing B lymphoblastoid cells, UC. Mutants with the greatest effect on binding were located in a portion of the molecule homologous to the first and second hypervariable regions of an antibody combining site. In addition, a panel of 12 anti-CD8 monoclonal antibodies were used to stain the 10 CD8 mutants, and amino acids that affected antibody binding were localized on the crystal structure of the BenceJones homodimer, REI . Support for an Ig-like structure of CD8 can be found in the pattern of substitutions affecting antibody binding. This work supports the similar tertiary structure of the CD8 a-terminal domain and an Ig variable domain.T he TCR-CD3 complex associates with CD8 or CD4 to form a multimeric complex interacting with peptide and HLA class I or HLA class II, respectively, during T cell activation . In addition to their function as adhesion molecules, CD8 and CD4 also serve as signalling molecules. The cytoplasmic domains of CD4 and CDSa bind to the NH2-terminal domain of the intracellular tyrosine protein kinase p56kk (1-3) . Antibody crosslinking of CD8 and CD4 to the TCR-CD3 complex leads to enhanced calcium flux and phosphorylation of a set of proteins, which includes the r chain of the TCR complex (4-6) . The ability of CD8 to induce these changes is dependent on its ability to associate with p56kk . CD8 and CD4 are also important for positive and negative selection in the thymus (7, 8). TCR specificity in T cell repertoire selection is determined by both the TCRa/(3 heterodimer and CD4 or CD8 accessory molecules (9, 10) .The human CD8 molecule is expressed either as an al a homodimer or as an a/(3 heterodimer. The homodimer is expressed exclusively on subsets of TCR-y/S cells and NK cells, and is co-expressed with CD80 on peripheral T cells and thymocytes . Individual human peripheral T cells can express varying amounts of CD8 a/a and alai complexes, and these appear to be differentially regulated upon T cell activation (11). CD8 expression can be induced on human CD4 cells upon activation with mitogens (12) and on murin...

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“…In addition, the ␣-chain of the CD8 coreceptor binds to the ␣3 domain of MHC-I (28 -32) with very low affinity (ϳ200 M in solution (33)). The precise way in which CD8 facilitates T cell activation is unclear, but it includes stabilization of the T cell-target contact and activation of lck (10,12,34,35). One model suggests that the TCR first engages the peptide MHC complex; this leads to lck activation and subsequent recruitment of CD8 into the multimolecular TCR/ CD3/MHC-I complex (33,36).…”

Section: Discussionmentioning

confidence: 99%

Soluble CD8 Attenuates Cytotoxic T Cell Responses Against Replication-Defective Adenovirus Affording Transprotection of Transgenes In Vivo

Peng

Falck-Pedersen

Elkon³

2000

The Journal of Immunology

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The T cell coreceptor, CD8, enhances T cell-APC interactions. Because soluble CD8α homodimers can antagonize CD8 T cell activation in vitro, we asked whether secretion of soluble CD8 would effect cytotoxic T cell responses in vivo. Production of soluble CD8 by a replication-defective adenovirus vector allowed persistent virus expression for up to 5 mo in C57BL/6 mice and protected a second foreign transgene from rapid deletion. Soluble CD8 selectively inhibited CD8 T cell proliferation and IFN-γ production and could also attenuate peptide-specific CD8 T cell responses in vivo. These finding suggest that gene vector delivery of soluble CD8 may have therapeutic applications.

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Cell-cell adhesion mediated by CD8 and MHC class I molecules

Cited by 405 publications

References 34 publications

Idiotype-induced T cell stimulation requires antigen presentation in association with HLA-DR molecules

Idiotype-induced T cell stimulation requires antigen presentation in association with HLA-DR molecules

Mutations in CD8 that affect interactions with HLA class I and monoclonal anti-CD8 antibodies.

Soluble CD8 Attenuates Cytotoxic T Cell Responses Against Replication-Defective Adenovirus Affording Transprotection of Transgenes In Vivo

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