title: Expression of the mouse MHC class Ib H2-T11 gene product, a paralog of H2-T23 (Qa-1) with shared peptide-binding specificity.
abstract: The mouse MHC class Ib gene H2-T11 is 95% identical at the DNA level to H2-T23, which encodes Qa-1, one of the most studied MHC class Ib molecules. H2-T11 mRNA was observed to be expressed widely in tissues of C57BL/6 mice, with the highest levels in thymus. To circumvent the availability of a specific mAb, cells were transduced with cDNA encoding T11 with a substituted α3 domain. Hybrid T11D3 protein was expressed at high levels similar to control T23D3 molecules on the surface of both TAP(+) and TAP(-) cells. Soluble T11D3 was generated by folding in vitro with Qa-1 determinant modifier, the dominant peptide presented by Qa-1. The circular dichroism spectrum of this protein was similar to that of other MHC class I molecules, and it was observed to bind labeled Qa-1 determinant modifier peptide with rapid kinetics. By contrast to the Qa-1 control, T11 tetramers did not react with cells expressing CD94/NKG2A, supporting the conclusion that T11 cannot replace Qa-1 as a ligand for NK cell inhibitory receptors. T11 also failed to substitute for Qa-1 in the presentation of insulin to a Qa-1-restricted T cell hybridoma. Despite divergent function, T11 was observed to share peptide-loading specificity with Qa-1. Direct analysis by tandem mass spectrometry of peptides eluted from T11D3 and T23D3 isolated from Hela cells demonstrated a diversity of peptides with a clear motif that was shared between the two molecules. Thus, T11 is a paralog of T23 encoding an MHC class Ib molecule that shares peptide-binding specificity with Qa-1 but differs in function.
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and.
authors: Lili
authors: L
authors: Chen
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and.
authors: Eduardo
authors: E
authors: Reyes-Vargas
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and.
authors: Hu
authors: H
authors: Dai
authors: ARUP Laboratories, Salt Lake City, UT 84112.
authors: Hernando
authors: H
authors: Escobar
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and.
authors: Brant
authors: B
authors: Rudd
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and.
authors: Jared
authors: J
authors: Fairbanks
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and.
authors: Alexander
authors: A
authors: Ho
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and.
authors: Mathew F
authors: MF
authors: Cusick
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and ARUP Laboratories, Salt Lake City, UT 84112.
authors: Attila
authors: A
authors: Kumánovics
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and ARUP Laboratories, Salt Lake City, UT 84112.
authors: Julio
authors: J
authors: Delgado
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and xiao.he@path.utan.edu peter.jensen@path.utah.edu.
authors: Xiao
authors: X
authors: He
authors: Department of Pathology, University of Utah, Salt Lake City, UT 84112; and ARUP Laboratories, Salt Lake City, UT 84112 xiao.he@path.utan.edu peter.jensen@path.utah.edu.
authors: Peter E
authors: PE
authors: Jensen
mesh_terms: D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology
chemical_list: D000939:Epitopes; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C032907:Q surface antigens