Specific Positive Selection of Lymphocytes

The population of thymus-derlved (T) lymphocytes reactive to strong histocompatibility (H) 1 alloantigens (HARC) is peculiar in two respects in comparison to lymphocytes~responsive to other antigens: first, the T cells reactive to any given strong H antigen outnumber by two to three orders of magnitude the T cells responsive to more conventional antigens (1-3); and secondly, the frequency of HARC to a given H alloanfigen is not increased as a consequence of immunization in vivo (4-6). Just how fundamental these distinctions are between immune reactivity to H alloantigens and other antigen systems is not presently known. For example, the high frequency of HARC raises the possibility that these cells are multipotential, having the capacity to react to several different antigenic determinants. I t is clear now that totipotentiality with respect to immune reactivity to H alloantigens can be excluded for HARC, since lymphocyte populations can be experimentally depleted of cells reactive to one H alloantigen, while retaining undiminished reactivity to other antigens (7-8). These "negative" selection experiments do not, however, allow conclusions concerning the ability of cells reactive to one H alloantigen to react to other H alloantigens or to conventional antigens. To examine this question it is essential to prepare pure populations of HARC with reactivity to a single H alloantigen so that the ability of these cells to react to other H alloantigens and to conventional antigens can be tested. This communication describes a procedure which appears to provide specific "positive" selection of cells reactive to chosen strong H alloantigens, and it also illustrates preliminary results obtained using this procedure. Previous studies have shown that parental strain T lymphocytes are induced to proliferate in the mixed lymphocyte interaction (MLI) when they are mixed with alloantigen-bearing cells derived from F1 animals (9), but disappear rapidly under the same culture conditions in the absence of antigen (2). This antigen-dependent survival of cells in the MLI could represent the progeny of lymphocytes specifically reactive to the priming antigens in the culture systems, and if so, these selected progeny should inherit the specific reactivity of their parents.