Evidence for specific association between class I major histocompatibility antigens and the CD8 molecules of human suppressor/cytotoxic cells

Blue, Marie‐Luise; Craig, Kimberly; Anderson, Paul; Branton, K R; Schlossman, Stuart F.

doi:10.1016/0092-8674(88)90204-8

Cited by 66 publications

(36 citation statements)

References 28 publications

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“…Moreover, we have demonstrated that the temporal co-existence of two conformational states allows misfolded MHC-I molecules to associate with other molecules and receptors, such as CD8␣␤. Early studies reporting the physical association between CD8␣␤ and MHC-I molecules used crosslinking reagents and antibodies against the CD8␣ chain (20,21). In our studies we also used anti-CD8␣ antibodies, and the levels of co-precipitated MHC-I molecules were very similar to these earlier studies even in the absence of cross-linking reagents.…”

Section: Fig 5 Mhc Class I Molecules Are Associated With Kinase Actsupporting

confidence: 65%

Misfolding of Major Histocompatibility Complex Class I Molecules in Activated T Cells Allows cis-Interactions with Receptors and Signaling Molecules and Is Associated with Tyrosine Phosphorylation

Santos

Powis

Arosa

2004

Journal of Biological Chemistry

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Knowledge of the origin and biochemical status of ␤ 2 -microglobulin-free or misfolded major histocompatibility complex (MHC)-I molecules is essential for understanding their pleiotropic properties. Here we show that in normal human T cells, misfolding of MHC-I molecules is turned on upon activation and cell division and is proportional to the level of proliferation. Immunoprecipitation showed that a number of proteins are associated with MHC-I heavy chains at the surface of activated T cells, including the CD8␣␤ receptor and the chaperone tandem calreticulin/ERp57, associations that rely upon the existence of a pool of HC-10-reactive molecules. Biochemical analysis showed that misfolded MHC-I molecules present at the cell surface are fully glycosylated mature molecules. Importantly, misfolded MHC-I molecules are tyrosine phosphorylated and are associated with kinase activity. In vitro kinase assays followed by reprecipitation indicated that tyrosine phosphorylation of the class I heavy chain is probably mediated by a Src tyrosine kinase because Lck was found associated with HC-10 immunocomplexes. Finally, we show that inhibition of tyrosine phosphorylation by using the Src-family tyrosine kinase inhibitor PP2 resulted in enhanced release of MHC-I heavy chains from the cell surface of activated T cells and a slight down-regulation of cell surface W6/32-reactive molecules. This study provides new insights into the biology of MHC-I molecules and suggests that tyrosine phosphorylation may be involved in the regulation of MHC-I misfolding and expression.

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Section: Fig 5 Mhc Class I Molecules Are Associated With Kinase Actsupporting

confidence: 65%

Misfolding of Major Histocompatibility Complex Class I Molecules in Activated T Cells Allows cis-Interactions with Receptors and Signaling Molecules and Is Associated with Tyrosine Phosphorylation

Santos

Powis

Arosa

2004

Journal of Biological Chemistry

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“…Peptide fingerprinting also showed the identity between the bands at 55-60 kDa (data not shown). The CD8 antigen itself focused as a series of six spots with a mass of32 kDa, a spectrum most probably related to sialylation and phosphorylation (25)(26)(27)(28).…”

Section: Resultsmentioning

confidence: 99%

“…Structurally, the antigen exists as a polypeptide of 32-35 kDa that can form various disulfide-linked multimers up to 200 kDa (23,24). CD8 also appears linked to the CD1 antigen on thymocytes and HLA class I antigens on peripheral blood lymphocytes (25)(26)(27)(28). Monoclonal antibodies to the CD8 antigen have been reported to either downregulate or potentiate the proliferation of T lymphocytes in a manner independent of MHC recognition (4,5,7).…”

mentioning

confidence: 99%

The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex.

Barber

Dasgupta

Schlossman

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

394

235

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Many mammalian receptors have been found to regulate cell growth by virtue of a protein-tyrosine kinase domain in their cytoplasmic tail. We recently described an association of the CD4 antigen with a T-cell-specific proteintyrosine kinase (p56"c"; formerly termed pp58lck; EC 2.7.1.112). This interaction represents a potential mechanism by which T-cell growth may be regulated and offers a model by which other members of the src family (products of c-src, c-yes, c-fgr, etc.) may interact with mammalian growth factor receptors. As in the case ofthe CD4 antigen, the CD8 antigen appears to serve as a receptor for nonpolymorphic regions of products of the major histocompatibility complex and has been implicated in the regulation of T-cell growth. In this study, we reveal that the human CD8 antigen is also associated with the T-cell-specific protein-tyrosine kinase (p56""k).

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“…This apparent "background" was not due to proteins nonspecifically sticking to the mAb-Sepharose columns since it was not observed in the control IL-2 receptor purifications. An increasing number of cell-surface molecules have been documented as associating or cocapping together-for instance, TCR af3 and CD3 (23), CD8 and class I MHC (33,34), CD4 and LFA-1 (35), and CD45 and a variety of independent cell-surface antigens (36,37). When the T cell binds to the specific APC, some of these molecules are reorganized with the cytoskeletal components into the site of membrane contact (11), thereby demonstrating their connection, either direct or indirect, with the cytoskeleton and with each other.…”

Section: Resultsmentioning

confidence: 99%

CD4 and CD8 molecules can physically associate with the same T-cell receptor.

Gallagher

Groth

Miller

1989

Proc. Natl. Acad. Sci. U.S.A.

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Evidence for specific association between class I major histocompatibility antigens and the CD8 molecules of human suppressor/cytotoxic cells

Cited by 66 publications

References 28 publications

Misfolding of Major Histocompatibility Complex Class I Molecules in Activated T Cells Allows cis-Interactions with Receptors and Signaling Molecules and Is Associated with Tyrosine Phosphorylation

Misfolding of Major Histocompatibility Complex Class I Molecules in Activated T Cells Allows cis-Interactions with Receptors and Signaling Molecules and Is Associated with Tyrosine Phosphorylation

The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex.

CD4 and CD8 molecules can physically associate with the same T-cell receptor.

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