Recognition of Epstein-Barr virus (EBV)-infected cells by T cell colonies from a human chimera: restriction by allogeneic determinants

Abstract

The anti-EBV T cell response was studied in a severe combined immunodeficiency patient (PS) who received two transplants of fetal liver cells. His peripheral blood mononuclear cells (PBMC) were incubated with EBV and cultured during 15 days. Eleven colonies were derived from the T lymphocytes causing the regression of the infected cell foci: nine were constituted with CD3+ CD4+ CD8- lymphocytes and two with CD3+ CD4- CD8+ cells. HLA typing of six colonies showed that two of them derived from the first transplant and four from the second one. The colonies killed the cells of the lymphoblastoid line (LCL) derived from the recipient (PS-LCL), but failed to kill the LCL matched with the transplants. With only one exception, they all lysed also the LCL derived from the mother or from the father, but they were ineffective on the EBV-negative lymphoblasts. Two colonies recognized determinants which did not appear to be HLA antigens, although they were shared by PS and by one of his parents, two (CD4- CD8+) reacted against the LCL which shared HLA-A3 or -A33 with PS-LCL, and four (CD4+ CD8-) lysed the LCL sharing HLA-A3, -A33 or -DR5 with PS-LCL, among which only one was demonstrated to interact directly with host HLA-class I determinants. These data indicate that T lymphocytes differentiating in contact with histo-incompatible determinants may express the capability to recognize viral antigens and to lyse virus-infected cells in the context of allogeneic MHC or non-MHC molecules.