The major objective of this proposal is to characterize further and define the humoral immune system of rhesus and pig-tailed macaques. These species are an invaluable and unique resource that are being used with increasing frequency for studies related to the pathogenesis, prophylaxis, diagnosis and therapy of a variety of human diseases. Rhesus and pig-tailed macaques are an important component of the NIH Regional Primate Research Center programs across the country and are essential to the HIV/SIV studies at the Centers and at numerous other NIH-funded institutions. Although cellular immune responses have been well characterized in macaques, limited information is available on their humoral immunity. The accurate definition of the humoral arm of the immune system, particularly and antibody repertoire, is imperative in order to validate the macaque model. To define the humoral immune system of these nonhuman primate species, we will analyze the macaque antibody repertoire at two different levels, genotypic phenotypic. Specifically, three specific aims are proposed to: 1) identify immunglobulin variable region genes and their products in rhesus and pig-tailed macaques; 2) identify immunoglobulin constant region genes and their products in rhesus and pig-tailed macaques; and 3) generate reagents specific for macaque immunoglobulin variable and constant regions and utilize these reagents to define antibody patterns in normal rhesus and pig-tailed macaques. Accomplishment of these specific aims will provide well-defined nonhuman primate models for understanding antibody-mediated protective and pathogenetic mechanisms and for the evaluation of the efficacy of novel immunointervention strategies.