A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides.
Unlike the highly polymorphic major histocompatibility complex (MHC) class Ia molecules, which present a wide variety of peptides to T cells, it is generally assumed that the nonpolymorphic MHC class Ib molecules may have evolved to function as highly specialized receptors for the presentation of structurally unique peptides. However, a thorough biochemical analysis of one class Ib molecule, the soluble isoform of Qa-2 antigen (H-2SQ7b), has revealed that it binds a diverse array of structurally similar peptides derived from intracellular proteins in much the same manner as the classical antigen-presenting molecules. Specifically, we find that SQ7b molecules are heterodimers of heavy and light chains complexed with nonameric peptides in a 1:1:1 ratio. These peptides contain a conserved hydrophobic residue at the COOH terminus and a combination of one or more conserved residue(s) at P7 (histidine), P2 (glutamine/leucine), and/or P3 (leucine/asparagine) as anchors for binding SQ7b. 2 of 18 sequenced peptides matched cytosolic proteins (cofilin and L19 ribosomal protein), suggesting an intracellular source of the SQ7b ligands. Minimal estimates of the peptide repertoire revealed that at least 200 different naturally processed self-peptides can bind SQ7b molecules. Since Qa-2 molecules associate with a diverse array of peptides, we suggest that they function as effective presenting molecules of endogenously synthesized proteins like the class Ia molecules.
Joyce
S
S
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461-1975.
Tabaczewski
P
P
Angeletti
R H
RH
Nathenson
S G
SG
Stroynowski
I
I
D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006183:H-2 Antigens / Q000737:chemistry / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015183:Restriction Mapping; D012995:Solubility; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C032907:Q surface antigens; D014867:Water