Abstract

The ability of the immune system to recognize and respond to specific antigens is the cornerstone of the adaptive immune response. The major cell responsible for directing and effecting these antigen-specific responses is the T lymphocyte, with its highly specific cell surface antigen receptor. This T cell receptor (TCR) is, however, unable to recognize its specific antigen in a native form. Instead, the TCRs recognize small peptide fragments that are produced from the complex structural and functional proteins of a pathogen by degradation. Following degradation, these short peptide fragments are presented to T cells in association with peptide-binding glycoproteins called MHC molecules. The recognition of this MHC-peptide complex by the TCR is a key step in eliciting and maintaining an appropriate and effective immune response to a foreign peptide. An appreciation of the function of MHC molecules is important in understanding individual and population susceptibility to infectious disease. This presentation reviews the role that MHC molecules play in the adaptive immune system and shows how a knowledge of the marine mammal MHC can be used in designing strategies against infectious disease in susceptible populations.

The organization and structure of the genes encoding the MHC molecules are major factors that allow the immune system to recognize such a vast array of antigens. Without the successful formation of the MHC-peptide-TCR complex, an antigen-specific immune response will not develop. In fact, pathogens which contain genes encoding structural proteins that escape MHC binding can evade the host immune system. Furthermore, in animal populations with limited MHC diversity, certain individuals may lack the MHC molecules needed to bind antigenic peptides from a particular pathogen, rendering them highly susceptible to infection with that agent. Over the past several years a number of marine mammal populations have suffered epidemic outbreaks of infectious disease. While the causal agents of many of these epidemics have been identified, the factors precipitating their virulence, and the associated high morbidity and mortality in certain populations, are less well understood. It is possible that each epidemic represents the emergence of a novel pathogen. Alternatively, since susceptibility to infection involves an interaction between pathogen exposure and host immune responses, these outbreaks could reflect a change in the immune status of some of our marine mammal populations. This change in immune status could arise from an exogenous immune suppressive agent such as a toxin or infectious agent, or may represent limited MHC diversity in certain species. This paper describes studies currently underway in our laboratory examining the MHC genotype, haplotype, and phenotype of the northern elephant seal and harbor seal. These studies are designed to examine the MHC-associated susceptibility of these pinnipeds to certain viral infections, and to identify common MHC haplotypes that may be used in designing vaccination strategies against emerging pathogens.