Antigen altered idiotype induces immune regulation implications for cancer, autoimmunity and AIDS (61.17)

Abstract

Abstract Antigen altered idiotype regulates specific immune responses. Mendelian segregation of a given +/- phenotype defines an immune response gene (IR-X) . Autoimmunity producing anti-self clones must be eliminated or specifically suppressed, so a large portion of the antigenic repertoire resembles allogeneic MHC molecules. Singer and Williams (Cell Immunol.1978: 4:1) proposed that exposure to many allogeneic HLA molecules could eventually overlap with important responses to pathogens, causing serious holes in the repertoire, some large enough to produce an acquired immunodeficiency syndrome (AIDS). The changes resulting from exposure to multiple incompatible allogeneic MHC molecules could also produce the opposite effect, an increase in a desirable immune response, or the allogeneic effect . IR-genes for histocompatible tumor resistance localized to the mouse MHC (Cancer Res. 1975;35:1586) The patient with HIV and AML, who was rendered free of both by transplantation of the right allogeneic stem cells (Blood,2010,Dec 8) supports our case. We propose that HIV is a unique and potent inducer of altered idiotype immune suppression. Explanation of the mechanism for synthetic antigens by Benacerraf (Nobel, 1980) and for viruses by Zinkernagel and Doherty (Nobel, 1986) followed from the idiotype network concept of Jerne (Nobel, 1984). Our attempt to relate these observations to the MHC and genetically controlled immune responses led us to the altered idiotype hypothesis.