Immune recognition of HLA molecules downmodulates CD8 expression on cytotoxic T lymphocytes.
An HLA-A2+ cytotoxic T lymphocyte (CTL) line restricted by HLA-A2 in recognition of an influenza B virus nucleoprotein (BNP) peptide uses the CD8 coreceptor in the recognition of this viral peptide. Incubation of these CTL with BNP peptide in the absence of antigen-presenting cells downmodulates CD8 alpha and CD8 beta expression and reduces their ability to lyse target cells without inducing self-lysis. CD8 downmodulation was dependent on peptide concentration, time of exposure, and T cell receptor specificity. Another viral peptide from the influenza A virus matrix protein interacting with HLA-A2 had no effect on CD8 expression. Upon further investigation, an anti-HLA class I monoclonal antibody (mAb), anti-HLA class II mAb, and HLA alloantisera were found to downmodulate CD8 alpha and CD8 beta expression and induce CTL nonresponsiveness without causing degranulation. When CD8 alpha and CD8 beta expression was modulated by viral peptide or anti-HLA mAbs, other cell surface molecules were unchanged. Finally, incubation of peripheral blood lymphocytes with these anti-HLA mAbs induced no change in CD8 expression on resting cells but did downmodulate it on mitogen-activated cells. These results suggest that T cell recognition of the HLA-A2-BNP peptide complex on neighboring CTL may be the mechanism for CD8 downmodulation induced by the BNP viral peptide. This mechanism may be important in clonal anergy.
Robbins
P A
PA
Institute for Molecular Medicine, John Radcliffe Hospital, Oxford, England.
McMichael
A J
AJ
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D016827:CD8 Antigens; D002460:Cell Line; D015536:Down-Regulation / Q000276:immunology; D005786:Gene Expression Regulation; D015789:HLA-A2 Antigen / Q000276:immunology / Q000502:physiology*; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D015789:HLA-A2 Antigen; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins