The monoclonal antibody KJ23a reacts with T cell receptors utilizing the VP segment Vt317a. T ceils bearing Vp17a+ receptors react with very high frequency with the MHC class II protein, IE. In this paper we show that T cells expressing Vpl7a are selectively eliminated from the peripheral T cell and mature thymocyte pool of mice expressing IE, but are present in expected numbers in the immature thymocyte population of such animals. These results show that in normal animals tolerance to self-MHC is due to clonal elimination rather than suppression. In addition, they indicate that tolerance induction may occur in the thymu8 at the time immature thymocytes are selected to move into the mature thymocyte pool.

The means by which the immune system discriminates between foreign antigens and potentially immunogenic self-antigens remains poorly understood. Classic experiments established that this tolerance to self-antigens is acquired during the development of the immune system within each individual (Owen, 1945; Billingham et al., 1956). Hence T cell and B cell receptors reactive to selfantigens are encoded in the germ line, but the activity of cells with these receptors is not usually apparent among mature functional lymphocytes. T cell tolerance to products of the major histocompatibility complex (MHC) is a particularly striking example of this phenomenon. T cells within an individual of a species mount a very strong response to products of foreign alleles of this extremely polymorphic complex (Fischer-Lindahl and Wilson, 1977) but fail to respond well to the products of self-MHC alleles. The mechanism of tolerance induction is unknown. One of the oldest hypotheses is that lymphocyte clones with self-reactivity are eliminated from the popuiation during a critical stage in development. However, based on the demonstration in several in vitro experimental systems of persistent self-reactive clones among mature lymphocytes (Smith and Pasternak, 1978; Battisto and Ponzio, 1981; Glimcher and Shevach, 1982) other hypotheses