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A shared MHC supertype motif emerges by convergent evolution in macaques and mice, but is totally absent in human MHC

Alessandro Sette1, John Sidney, Scott Southwood

  • 1Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.

Immunogenetics
|February 11, 2012
PubMed

Insights

Researchers identified a unique Major Histocompatibility Complex (MHC) peptide-binding motif in rhesus macaques, characterized by glycine at the second position. This finding, termed the "G2" motif, is absent in humans and offers new insights into SIV infection and vaccine development.

Area of Science:

  • Immunology
  • Primate models of infectious disease
  • Molecular biology

Background:

  • The SIV-infected rhesus macaque is a key model for AIDS research, crucial for understanding disease pathogenesis and evaluating vaccine efficacy.
  • Major Histocompatibility Complex (MHC) molecules and their peptide-binding motifs are vital for deciphering cellular immune responses, infection outcomes, and vaccine effectiveness.

Purpose of the Study:

  • To characterize the MHC:peptide-binding motif of the Mamu-B*039:01 allele in Chinese rhesus macaques.
  • To investigate the structural basis and evolutionary significance of unique peptide-binding motifs in nonhuman primate MHC molecules.

Main Methods:

  • Detailed characterization of the Mamu-B*039:01 MHC allele and its peptide-binding preference.
  • Identification and analysis of antigenic peptides associated with Mamu-B*039:01.
  • Comparative analysis of MHC pocket structures and binding motifs across species, including rhesus macaques, mice, and humans.

Main Results:

  • A unique MHC:peptide-binding motif, featuring glycine at the second position (G2 motif), was identified for Mamu-B*039:01.
  • This G2 motif was also found in Mamu-B*052:01 from Indian rhesus macaques and associated with specific B pocket residues, a structure absent in human HLA class I alleles.
  • Evolutionary analysis suggests common ancestry for macaque G2 alleles and convergent evolution with murine alleles, indicating a novel supertype motif not present in humans.

Conclusions:

  • The characterization of the G2 motif in rhesus macaques provides novel insights into nonhuman primate immunology and MHC diversity.
  • This unique motif, absent in humans, highlights differences in immune recognition between macaques and humans, impacting SIV research and vaccine design.
  • The findings reveal a new MHC supertype motif in nonhuman primates and mice, crucial for understanding cellular immunity in these models.

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