Target antigens

Primary MLRs are directed almost exclusively to gene products of the MHC. The MHC encodes two broad classes of cell surface molecules, termed class

I and class II. Class I molecules are expressed on virtually all cell types. Class II molecules, by contrast, show a much more limited distribution with high expression restricted to B cells, macrophages and dendritic cells; in humans, class II molecules are expressed on T cells, but only after activation. Both classes of MHC molecules show extensive polymorphism. According to the literature, class II alloanti-gens provide a much stronger stimulus for primary MLRs than class I alloantigens. As discussed later, however, it has recently become apparent that class I alloantigens can elicit strong MLRs under certain conditions.

The mouse provides the one exception to the rule that MLRs are directed almost exclusively to MHC alloantigens. In this species, very powerful MLRs can be stimulated by Mis determinants. These antigens display limited polymorphism and represent endogenous superantigens encoded by mouse mammary tumor virus (mtv) genes. Only a small proportion of mtv antigens elicit strong primary MLRs; these particular mtv antigens are termed Mis antigens. Since mtv antigens bind to T cell receptor V(i epitopes, MLR to mtv antigens are V0 specific. It should be noted that H-2 and Mis molecules are unrelated and are encoded on different chromosomes. To date, Mis molecules have not been described in other species.

For MHC alloantigens, there is increasing evidence that MLRs are not directed to MHC epitopes per se but to a broad array of self peptides bound to MHC molecules. Most of these peptides are presumably derived through breakdown of various intracellular proteins involved in cell metabolism.

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