Biological Role of Major Transplantation Antigens in T Cell Self-recognition: Possible Consequences in Clinical Medicine

Abstract

During the past years, our ideas on immunity have changed fundamentally: Thymus derived lymphocytes (T cells) express two specificities, one for foreign antigenic determinants and one for a cell-surface self-determinant coded by the major histocompatibility gene complex (MHC) i.e. T cells are restricted. These findings have been influencing basic immunology and are relevant to our understanding of immune phenomena in infectious disease:

• 1. T cell restriction determines what antigens are immunogenic.

• 2. T cell restriction has to be taken into account for in vitro testing of cell-mediated immunity.

• 3. The specificity for self-MHC of T cells is determined during maturation in the thymus; therefore reconstitution of immunodeficiency depends on thymus grafts and bone marrow stem cells sharing MHC determinants.

• 4. T cell restriction may well give us one key to understand why some disease susceptibilities may be linked to the MHC (HLA in human, H-2 in mice).

Diseases whose susceptibility is associated with certain alleles of MHC reflect (a) immuno-pathologic effects of T cells, (b) T cell effector function determined by the restricting MHC products and (c) an intimate link between MHC polymorphism and size of the T cell receptor repertoire. Immunopathological T cell-dependent diseases therefore are likely to be associated with the MHC, and MHC association signals T cell-mediated immunopathology. Since the balance between infectious agents and immune reactivity determines disease outcome it is of great importance to understand the parameters of the infectious agents and of the host influencing this equilibrium before attempting to manipulate immunopathological disease with immunostimulant or immunosuppressive treatments.