Dw subtypes of serologically defined DR-DQ specificities restrict recognition of cytomegalovirus

Abstract

We have investigated the relationship between serologically defined (Ia) and T lymphocyte-defined (LD/Dw) determinants in restricted recognition of cytomegalovirus (CMV) by human T lymphocytes. T lymphocytes isolated from CMV seropositive individuals expressing DQw3/DR4/Dw4 antigens were "sensitized" to CMV in vitro; CMV-specific blasts were isolated and tested for their ability to recognize CMV presented by cells expressing different DR4-associated Dw antigens (i.e., Dw4, Dw10, Dw13, Dw14, and Dw15). Similar studies were also performed using T lymphocytes from individuals expressing DQw1/DR2/Dw2 specificities and antigen presenting cells (APC) expressing the DR2-associated Dw/LD subtypes, Dw2, Dw12, and LD-MN2. CMV-specific T cell blasts were used as responding cells in order to reduce nonspecific background alloresponses which occur with allogeneic APC. In all cases it was found that the determinants involved in restricted recognition of CMV were subtypic to the DR-associated Ia specificities. To distinguish whether Dw specificities associated with DQ or with DR molecules, or both, were involved in these responses, we used anti-DR (L243) and an anti-DQwl (S3/4) monoclonal antibodies (MoAb) to block CMV-specific responses. Both MoAb significantly blocked responses, suggesting that determinants associated with both DR and DQ molecules are involved in restricted recognition of CMV by T cells.