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.
Thammavongsa
Vilasack
V
Department of Microbiology and Immunology, University of Michigan Medical School, 5641 Medical Science Building II, Ann Arbor, MI 48109-0620, USA.
Schaefer
Malinda
M
Filzen
Tracey
T
Collins
Kathleen L
KL
Carrington
Mary
M
Bangia
Naveen
N
Raghavan
Malini
M
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