HLA supertypes contribute in HIV type 1 cytotoxic T lymphocyte epitope clustering in Nef and Gag proteins.
Induction of HIV-1-specific cytotoxic T lymphocyte (CTL) responses largely depends upon the presentation of CTL epitopes to the CD8(+) T cells aided by a large number of different HLA class I alleles. Although several studies showed the clustering pattern of HIV-1 CTL epitopes, the underlying reason for this tendency remains unresolved. Moreover, the hypothesis that the CTL epitope clusters tend to coincide with the conserved and hydrophobic regions of HIV-1 proteins has been challenged in recent times. The present study aims to characterize and compare the HIV-1 CTL epitope clusters in terms of restricting HLA alleles, hydrophobicity, and sequence conservation in a proteome-wide manner by including a large number of experimentally validated CTL epitopes from the HIV Molecular Immunology Database. CTL epitope cluster distribution analysis in a proteome-wide manner revealed that only two HIV-1 proteins, namely Nef and Gag, have significant cluster-forming capacity where their epitope localization coincides with the hydrophobic and conserved regions. Furthermore, analyses of proteasomal cleavage sites and HLA anchoring motif frequencies in the epitope-dense regions highlighted the role of specific HLA supertypes such as HLA B*07, HLA B*58, HLA A*02, and HLA A*03 in selecting the hydrophobic and conserved amino acid positions within Nef and Gag proteins to be presented as epitopes. Based on our results, we hypothesize that the cluster-forming tendency of HIV-1 CTL epitopes is not a proteome-wide feature confined to Nef and Gag proteins. Their cluster-forming tendency largely depends on the host HLA alleles that contribute significantly in selecting functionally constrained hydrophobic regions within the HIV-1 proteome.
Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Dhaka, Dhaka 1000, Bangladesh. sajib@univdhaka.edu
Sajib
S
Chakraborty
Taibur
T
Rahman
Rajib
R
Chakravorty
Alison
A
Kuchta
Atai
A
Rabby
Munsi
M
Sahiuzzaman
D017951:Antigen Presentation; D017124:Conserved Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus