Immunogenetics

, Volume 61, Issue 11, pp 703–716

Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503

  • Vilasack Thammavongsa
  • Malinda Schaefer
  • Tracey Filzen
  • Kathleen L. Collins
  • Mary Carrington
  • Naveen Bangia
  • Malini Raghavan
Original Paper

DOI: 10.1007/s00251-009-0399-2

Cite this article as:
Thammavongsa, V., Schaefer, M., Filzen, T. et al. Immunogenetics (2009) 61: 703. doi:10.1007/s00251-009-0399-2

Abstract

Residue 116 of major histocompatibility complex (MHC) class I heavy chains is an important determinant of assembly, that can influence rates of ER-Golgi trafficking, binding to the transporter associated with antigen processing (TAP), tapasin dependence of assembly, and the efficiency and specificity of peptide binding. Here, we investigated assembly and peptide-binding differences between HLA-B*3501(S116) and HLA-B*3503(F116), two alleles differing only at position 116 of the MHC class I heavy chain, that are associated respectively with normal or rapid AIDS progression. A reduced intracellular maturation rate was observed for HLA-B*3503 in HIV-infected and uninfected cells, which correlated with enhanced binding of HLA-B*3503 to TAP. No significant differences in the intrinsic efficiency of in vitro peptide binding by HLA-B*3501 and HLA-B*3503 were measurable with several common peptides or peptide libraries, and both allotypes were relatively tapasin-independent for their assembly. However, thermostability differences between the two allotypes were measurable in a CD4+ T cell line. These findings suggest that compared to HLA-B*3501, a reduced intracellular peptide repertoire for HLA-B*3503 could contribute to its slower intracellular trafficking and stronger association with rapid AIDS progression.

Keywords

MHC class ITapasinAntigen presentation/processingTAP transporterHLA-B*3501HLA-B*3503HLA-B*4402HLA-B*4405HLA-B*5701

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Vilasack Thammavongsa
    • 2
  • Malinda Schaefer
    • 2
  • Tracey Filzen
    • 1
  • Kathleen L. Collins
    • 1
  • Mary Carrington
    • 3
  • Naveen Bangia
    • 4
  • Malini Raghavan
    • 1
  1. 1.Department of Microbiology and ImmunologyUniversity of Michigan Medical SchoolAnn ArborUSA
  2. 2.Graduate Program in ImmunologyUniversity of Michigan Medical SchoolAnn ArborUSA
  3. 3.Cancer and Inflammation ProgramLaboratory of Experimental ImmunologyFrederickUSA
  4. 4.Department of ImmunologyRoswell Park Cancer InstituteBuffaloUSA