The guinea pig I region. II. Functional analysis.

Abstract

We have examined whether an association exists between specific Ia antigen genes and Ir genes which are encoded within the same haplotype. Functionally monospecific sera to the Ia antigens of the guinea pig MHC were selective in their ability to inhibit antigen-specific T-cell proliferation and we were thus able to demonstrate an association between individual Ia specificities and specific Ir genes. The results of these studies in inbred animals were confirmed by examining the association of Ir genes and Ia antigens in the outbred guinea pig population. Of great interest was the observation that antisera made against cross-reactive Ia antigens of strains lacking specific Ir genes would still inhibit immune responses of strains possessing the Ir gene, if the Ir gene was associated with that Ia antigen in the responder strain.

The Immune Response Genes of the Major Histocompatibility Complex

“…Conversely, responsiveness to GT, which is a property of strain 13 guinea pigs, is associated in random bred animals with the presence of one of the specificities detected by strain 2 alloantisera on strain 13 guinea pig lymphocytes (Bluestein et al 1971c). Recent studies by Shevach et al (1977) extended these early findings using monospedfic anti-la sera. These investigators studied the proliferative response in vitro of peritoneal lymphocytes from animals sensitized to antigens under the control of specific Ir genes and investigated the ability of specific anti-la sera to inhibit this response.…”

Experimental Beryllium-Induced Lung Disease

“…Relationships between immune response capacity and composition of the la region of the major histocompatibility complex have been es tablished in strains 2 and 13 guinea pigs, which differ only with respect to la profile [12,13]. In addition, differences in susceptibility to diseases having an im munologic basis are also well known in strains 2 and 13, as for example experimental allergic encephalo myelitis, which is more readily induced by homolo gous myelin basic protein in strain 13 than in strain 2 animals [14].…”

The guinea pig i-region. A functional analysis of Ia-Ir associations

“…Recently, the availability of monospecific antisera to most of the Ia antigens of the GPLA complex has allowed us to demonstrate that an association exists between individual Ia specificities and specific Ir genes which are encoded within the same haplotype [42]. As previously demonstrated, anti-Ia.2,4 or anti-Ia.l,3,7 sera Studies with antisera to the cross-reactive antigens Ia.5 and Ia.6 supported the concept that it is antibodies to Ia antigens rather than antibodies to unique determinants of Ir gene products that are responsible for the inhibition of T cell proliferation.…”