Reactivity patterns of class I HLA monoclonal antibodies that distinguish three species of macaques.

The reactivity of a panel of 40 monoclonal antibodies (mAb) specific for HLA class I antigens was assessed in 117 unrelated Macaca mulatta (Mm), with a standard microcytotoxicity assay, in order to compare phenotypic frequencies with those previously reported for M. fascicularis (Mfl) and M. nemestrina (Mn). Based on the reactivity with HLA typed human cell panels, the epitopes recognized by these mAb in macaques were classified as nonpolymorphic, polymorphic "public," and polymorphic "private." Nei's genetic identity (I) and distance (D) formulae were applied to estimate I and D between each of the macaque species and between each macaque species and humans. The HLA nonpolymorphic epitopes emerged as spcies-specific determinants, as all three macaque species showed clear differences from each other and from humans in the frequency of occurrence in population samples. From our previous serologic study and from published sequence data, it is evident that the major histocompatibility complex (MHC) is highly conserved in primate evolution. Ninety percent of the mAb reacted at a similar frequency in either two or three macaque species. With few exceptions, the mAb reacted at a greater frequency in humans than in macaques. Concerning private HLA class I epitopes, we have previously speculated that the human MHC class I polymorphisms probably predate the diversification of macaque-human lineages, and hence would be highly conserved. However, the inconsistent pattern of occurrence of human monomorphic epitopes among the macaque species suggests that a complex explanation is required. One possibility is that HLA monomorphic epitopes are invariant in humans because of their yet unknown functional role; however, this explanation loses some force because of the inconsistent pattern of occurrence among three closely related species of Macaca. However, we favor a second possibility, i.e., that the monomorphic epitopes in humans might be the result of the accumulated neutral mutations and are not subjected to functional constraints. This explanation seems to fit the inconsistent pattern of occurrence of these epitopes among macaques.