Does intra-individual major histocompatibility complex diversity keep a golden mean?

Abstract

An adaptive immune response is usually initiated only if a major histocompatibility complex (MHC) molecule presents pathogen-derived peptides to T-cells. Every MHC molecule can present only peptides that match its peptide-binding groove. Thus, it seems advantageous for an individual to express many different MHC molecules to be able to resist many different pathogens. However, although MHC genes are the most polymorphic genes of vertebrates, each individual has only a very small subset of the diversity at the population level. This is an evolutionary paradox. We provide an overview of the current data on infection studies and mate-choice experiments and conclude that overall evidence suggests that intermediate intra-individual MHC diversity is optimal. Selective forces that may set an upper limit to intra-individual MHC diversity are discussed. An updated mathematical model based on recent findings on T-cell selection can predict the natural range of intra-individual MHC diversity. Thus, the aim of our review is to evaluate whether the number of MHC alleles usually present in individuals may be optimal to balance the advantages of presenting an increased range of peptides versus the disadvantages of an increased loss of T-cells.

Figure 1

Frequency distribution of the number of MHC II β-alleles per individual in 144 stickleback fish from a lake population. Adapted from Reusch et al. (2001).

Figure 2

The exponential decrease of the size of the mature TCR repertoire R(M) (given by (equation (4.3)) with R₀=10⁹; p^*=0.2) with increasing intra-individual MHC diversity M depicted for three scenarios with different stringencies of negative selection (dotted line, n^*=0.25; dashed line, n^*=0.5; solid line, n^*=0.9).

Figure 3

The probability P_i (given by equation (4.1)) that a response of the adaptive immune system against a pathogen is initiated plotted as a function of the intra-individual MHC diversity M for three scenarios with different stringencies of negative selection (dotted curve, n^*=0.25; dashed curve, n^*=0.5; solid curve, n^*=0.9). Parameter values in equation (4.1) are q=0.02; r=10⁻⁵; e=10; R₀=10⁹.