A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides

Sebastian Joyce, Piotr Tabaczewski, Ruth Hogue Angeletti, Stanley G. Nathenson, Iwona Stroynowski

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)579-588
Number of pages10
JournalJournal of Experimental Medicine
Volume179
Issue number2
StatePublished - Feb 1 1994

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Major Histocompatibility Complex
Peptides
Leucine
Actin Depolymerizing Factors
Peptide T
Ribosomal Proteins
Asparagine
Glutamine
Histidine
Protein Isoforms
Proteins
Ligands
T-Lymphocytes
Light
Antigens

ASJC Scopus subject areas

  • Immunology

Cite this

A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides. / Joyce, Sebastian; Tabaczewski, Piotr; Angeletti, Ruth Hogue; Nathenson, Stanley G.; Stroynowski, Iwona.

In: Journal of Experimental Medicine, Vol. 179, No. 2, 01.02.1994, p. 579-588.

Research output: Contribution to journalArticle

Joyce, Sebastian ; Tabaczewski, Piotr ; Angeletti, Ruth Hogue ; Nathenson, Stanley G. ; Stroynowski, Iwona. / A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides. In: Journal of Experimental Medicine. 1994 ; Vol. 179, No. 2. pp. 579-588.
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