AbstractA series of human T lymphocyte clones showing specific responses for major histocompatibility complex‐encoded alloantigens were isolated from a single culture. They were classified into distinct functional groups based on measurement of alloantigen‐specific proliferation and cytotoxicity. Surface antigen expression on these clones was analyzed using a panel of monoclonal antibodies specific for T cell differentiation antigens and for Ia‐like antigens. Four distinct groups were identified based on the Leu series of differentiation antigens: (a) Leu1+,2+,3+,4+; (b) Leu1+,3+,4+; (c) Leu1+,2+,4+; and (d) Leu2+,4+. Functionally distinct clones showed not only differential expression of Leu2 and Leu3, antigens which had previously been shown to distinguish helper/inducer and cytotoxic/suppressor cells, but also of Leu1, an antigen classified as a common T cell marker. All of the clones were found to express Ia antigens as detected by three framework monoclonal antibodies, but none were found to express a determinant associated with the DR3 allospecificity, although it was found on normal B lymphocytes and a B cell line established from the HLA‐DR3 individual from whom these clones were derived.