Self-restricted primary human histocompatibility leukocyte antigen (HLA)-specific cytotoxic T lymphocytes.
The specificity of self MHC-restricted T cells responding to peptide fragments of processed antigen has been well characterized. However, the means by which alloreactive T lymphocytes recognize MHC alloantigen remain poorly understood. We now provide evidence that the recognition of class I human leukocyte antigen (HLA) alloantigen by alloreactive cytotoxic T lymphocytes (CTL) induced in primary mixed lymphocyte cultures is class I HLA-restricted to a great extent. This is shown by the 'split-well' limiting dilution assay using third party target cells bearing a stimulating class I HLA alloantigen either in (i) the presence or (ii) the absence of class I HLA antigen(s) which is shared with the responder. Alloreactive CTL were found which recognize stimulator class I HLA alloantigen on the first but not on the second type of target cells. The results show that, in contrast to the traditional view, a large proportion of the alloreactive CTL against class I HLA alloantigen generated in primary mixed lymphocyte cultures is self class I HLA-restricted.
Breur-Vriesendorp
B S
BS
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Ivanyi
P
P
D002478:Cells, Cultured; D003429:Cross Reactions; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007519:Isoantigens