A subpopulation of CD8+ T cells specific for melanocyte differentiation antigens expresses killer inhibitory receptors (KIR) in healthy donors: evidence for a role of KIR in the control of peripheral tolerance.
In cancer patients, NK cell inhibitory receptors (IR) are expressed on a fraction of melanoma-specific lymphocytes with a unique reactivity for tumor antigens derived from normal, nonmutated genes (differentiation antigens). It is presently not known whether expression of these receptors is induced during an immune response against melanoma cells or whether these receptors can be found on T cells harboring a self specificity for such differentiation antigens in healthy donors. By analyzing short-term cultures of CD8+ T cells primed in vitro with melanocyte differentiation antigens, we found expression of NK cell receptors on a small but consistent fraction of CD8+ T cells derived from healthy donors. Both long and short forms of NK cell receptors were expressed. Interestingly, only long forms were functional and inhibited effector functions (cytotoxicity and IFN-gamma production) of these CD8+ T cells. Short forms were devoid of any detectable activating function. The presence of T cells specific for differentiation antigens and expressing NK cell receptors, with an exclusive inhibitory function, in healthy donors strengthens the notion that IR may serve to control T cell tolerance to some peripheral antigens.
Huard
B
B
The R.W. Johnson Pharmaceutical Research Institute, San Diego, USA. huard@cmu.unige.ch
Karlsson
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D058965:MART-1 Antigen; D008544:Melanocytes / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D054340:Receptors, KIR; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; D015236:HLA-C Antigens; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D014442:Monophenol Monooxygenase