Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503.
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.
Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Science Building II, Ann Arbor, MI 48109-0620, USA.
Vilasack
V
Thammavongsa
Malinda
M
Schaefer
Tracey
T
Filzen
Kathleen L
KL
Collins
Mary
M
Carrington
Naveen
N
Bangia
Malini
M
Raghavan
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism / Q000821:virology; D000483:Alleles; D016367:Baculoviridae / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006056:Golgi Apparatus / Q000378:metabolism; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism*; D015797:HLA-B35 Antigen; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D042541:Intracellular Space / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015235:HLA-B Antigens; C500431:HLA-B*35:01 antigen; D015797:HLA-B35 Antigen; D026901:Membrane Transport Proteins; D010455:Peptides; C073119:TAP1 protein, human; C107762:tapasin