Genetically defined non-human primates are imposrtant in biomedical research for preclinical trials and as models for human diseases. Knowledge of the major histocompatibility complex is essential for most immunogenetic investigations. Among primates, the MHC is defined only in Rhesus, Chimpanzee and the Human species. The former two species are not available in sufficient numbers for many types of studies. In contrast cynomolgus macaques are more readily available and at a lower cost. These animals are increasingly important in studies of transplantation, especially for bone marrow graft research. Unfortunately, the MHC in this species was undefined until the current study was initiated except for work carried out by Dr. Morita for the Japan NIH and, as yet, unreported. Both alloantisera and mouse monoclonal antibodies will be used in this project. The long range objective of the present proposal is to define the Class I, Class II and Class III products of the MHC in M. fascicularis, designated CyLA, to determine the role of this polymorphic system in transplantation and disease, especially autoallergic disease. The first task is to produce serologic and cellular reagents capable of recognizing the alloantigenic products of the loci encoded by the CyLA system. Cytotoxic alloantisera will be produced by immunization with partially matched skin grafts and blood cells. Antisera which are operationally monospecific or oligospecific will be selected for extensive testing in unrelated and related animals in order to (a) define alleles, (b) determine gene frequencies, (c) identify linkage disequilibria and (d) the map order and recombination distances between loci. The major MLC locus, which controls proliferataive responses in primary allogenic cultures, will be characterized by use of homozygous typing cells obtained from consanguineous animals and animals matched for B-lymphocyte antigens in serologic tests. Both population studies on more than 300 animals and segregation studies in harem style breeding units will be conducted. The serological reagents to be produced will be able to recognize the majority of Class I and Class II allospecificities by the standard NIH cytotoxicity test and will constitute a reference bank of antisera for standardization of CyLA-A,B, and DR reagents. Skin graft survival times in groups of animals that are mismatched for 0,1,2 haplotypes will be determined. In collaboration with Dr. O'Reilly at Sloan-Kettering, the role of CyLA in resistance to BM survival will be studied.
