The Journal of Immunology, Vol 145, Issue 1 36-45, Copyright © 1990 by American Association of Immunologists

ARTICLES

Human T cell receptor-gamma delta-expressing T-cell lines recognize MHC- controlled elements on autologous EBV-LCL that are not HLA-A, -B, -C, - DR, -DQ, or -DP

V Lam, R DeMars, BP Chen, JA Hank, S Kovats, P Fisch and PM Sondel
Department of Human Oncology, University of Wisconsin, Madison 53792.

HLA-loss variants of an EBV-transformed B lymphoblastoid cell line (EBV- LCL) 721 were used to investigate whether human MHC molecules other than known class I or class II were involved in autologous T cell responses. Bulk lymphocyte cultures of purified T cells primed to an autologous variant EBV-LCL that fails to express HLA-class II and has reduced cell surface HLA-class I expression, and oligoclonal TCR-gamma delta-bearing lines derived from them, could lyse both this EBV-LCL and an independently derived, class II expressing autologous variant EBV- LCL that bears no HLA-A, -B, or -C, suggesting the presence of additional HLA-like restriction elements. Cold target inhibition of cytolysis mediated by these lines indicated that a shared or cross- reactive MHC controlled restriction element other than the known MHC determinants was retained by the EBV-LCL variants. Single-cell derived clones from these T cell lines which expressed only the TCR-gamma delta showed this same target cell specificity pattern, proving recognition of MHC-controlled determinants by autologous gamma delta T cells. Anti- gamma delta antibody could inhibit cytolysis by the gamma delta- expressing lines, suggesting that the TCR-gamma delta was involved in recognition of the EBV-LCL targets. Flow cytometric analysis with separate HLA-reactive antibodies indicated that the restriction element for these cytolytic responses is a molecule serologically cross- reactive with HLA-B and -C Ag, yet is a determinant that cannot be HLA- A, -B, -C, -DR, -DQ or -DP.