Allogeneic T cell activation triggering by MHC class I antigens.
The role of MHC-encoded class I molecules in allogeneic activation and proliferation of human T lymphocytes was investigated. The study was performed by using primary mixed culture of lymphocytes from MHC recombinant siblings identical for MHC class II Ag (DR, DP, DQ) and displaying MHC class I disparity. The results indicate that such allogeneic combination is sufficient to trigger early activation steps within responder T cells without promoting a significant proliferation. After MHC class I allosensitization, a significant proportion of cells entered the cell cycle (G0----G1). The stimulatory potential of MHC class I Ag was further stressed by the specific induction on responder cells of IL-2R (22% T cell activation Ag positive). Under the same experimental conditions, transferrin receptor expression and IL-2 activity were not detectable. This is consistent with the low T cell proliferation. Exogenous rIL-1 did not improve IL-2 production and the subsequent T cell proliferation indicating that these two events were not associated with a defective accessory cell function involving IL-1 release. MHC class I disparity can also prime precursor CTL to differentiate into IL-2-dependent functional MHC restricted cytotoxic T cells. Conversely IFN-gamma had no effect. Addition to the culture of W6/32, a mAb specifically directed against a monomorphic determinant on human class I HLA-A, -B, and -C Ag was able to block all these activation events. These data clearly indicate a role of HLA class I Ag involvement in the early events triggering allogeneic T cell activation.
Chouaib
S
S
Laboratoire d'Immunologie, UA1156 CNRS, Villejuif, France.
Bensussan
A
A
Termijtelen
A M
AM
Andreeff
M
M
Marchiol-Fournigault
C
C
Fradelizi
D
D
Dupont
B
B
D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005260:Female; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007399:Interphase; D008213:Lymphocyte Activation; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006680:HLA Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7