Compression of functional space in HLA-A sequence diversity

Bing Zhao; Adrian Eak H. Png; Ee Chee Ren; Prasanna R. Kolatkar; Venkatarajan Subramaniam Mathura; Meena Kishore Sakharkar; Pandjassarame Kangueane

doi:10.1016/S0198-8859(03)00078-8

Compression of functional space in HLA-A sequence diversity

Bing Zhao, Adrian Eak H. Png, Ee Chee Ren, Prasanna R. Kolatkar, Venkatarajan Subramaniam Mathura, Meena Kishore Sakharkar, Pandjassarame Kangueane^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

The major histocompatibility complex (MHC) is highly polymorphic and more than 1500 human MHC alleles are known to date. These alleles do not bind to a given peptide with identical affinity. Although MHC alleles are functionally related, it is difficult to quantify the functional variation between them. Three-dimensional structures of known MHC-peptide (MHCp) complexes suggest that specific peptide residues bind selectively to functional pockets in the binding groove. From a set of known MHCp structures we identified 21 critical polymorphic functional residue positions (CPFRP) that significantly reduced functional pocket variability to just 189 among 212 HLA-A alleles. Interestingly 101 HLA-A alleles clustered into 29 clusters such that the six functional pockets formed by the CPFRPs are identical within the cluster.

Original language	English
Pages (from-to)	718-728
Number of pages	11
Journal	Human Immunology
Volume	64
Issue number	7
DOIs	https://doi.org/10.1016/S0198-8859(03)00078-8
Publication status	Published - 1 Jul 2003
Externally published	Yes

Keywords

Functional pocket
MHC
Peptide binding

Access to Document

10.1016/S0198-8859(03)00078-8

Cite this

@article{e94509becb894c218d34e043fefda1a5,

title = "Compression of functional space in HLA-A sequence diversity",

abstract = "The major histocompatibility complex (MHC) is highly polymorphic and more than 1500 human MHC alleles are known to date. These alleles do not bind to a given peptide with identical affinity. Although MHC alleles are functionally related, it is difficult to quantify the functional variation between them. Three-dimensional structures of known MHC-peptide (MHCp) complexes suggest that specific peptide residues bind selectively to functional pockets in the binding groove. From a set of known MHCp structures we identified 21 critical polymorphic functional residue positions (CPFRP) that significantly reduced functional pocket variability to just 189 among 212 HLA-A alleles. Interestingly 101 HLA-A alleles clustered into 29 clusters such that the six functional pockets formed by the CPFRPs are identical within the cluster.",

keywords = "Functional pocket, MHC, Peptide binding",

author = "Bing Zhao and Png, \{Adrian Eak H.\} and Ren, \{Ee Chee\} and Kolatkar, \{Prasanna R.\} and Mathura, \{Venkatarajan Subramaniam\} and Sakharkar, \{Meena Kishore\} and Pandjassarame Kangueane",

year = "2003",

month = jul,

day = "1",

doi = "10.1016/S0198-8859(03)00078-8",

language = "English",

volume = "64",

pages = "718--728",

journal = "Human Immunology",

issn = "0198-8859",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - Compression of functional space in HLA-A sequence diversity

AU - Zhao, Bing

AU - Png, Adrian Eak H.

AU - Ren, Ee Chee

AU - Kolatkar, Prasanna R.

AU - Mathura, Venkatarajan Subramaniam

AU - Sakharkar, Meena Kishore

AU - Kangueane, Pandjassarame

PY - 2003/7/1

Y1 - 2003/7/1

N2 - The major histocompatibility complex (MHC) is highly polymorphic and more than 1500 human MHC alleles are known to date. These alleles do not bind to a given peptide with identical affinity. Although MHC alleles are functionally related, it is difficult to quantify the functional variation between them. Three-dimensional structures of known MHC-peptide (MHCp) complexes suggest that specific peptide residues bind selectively to functional pockets in the binding groove. From a set of known MHCp structures we identified 21 critical polymorphic functional residue positions (CPFRP) that significantly reduced functional pocket variability to just 189 among 212 HLA-A alleles. Interestingly 101 HLA-A alleles clustered into 29 clusters such that the six functional pockets formed by the CPFRPs are identical within the cluster.

AB - The major histocompatibility complex (MHC) is highly polymorphic and more than 1500 human MHC alleles are known to date. These alleles do not bind to a given peptide with identical affinity. Although MHC alleles are functionally related, it is difficult to quantify the functional variation between them. Three-dimensional structures of known MHC-peptide (MHCp) complexes suggest that specific peptide residues bind selectively to functional pockets in the binding groove. From a set of known MHCp structures we identified 21 critical polymorphic functional residue positions (CPFRP) that significantly reduced functional pocket variability to just 189 among 212 HLA-A alleles. Interestingly 101 HLA-A alleles clustered into 29 clusters such that the six functional pockets formed by the CPFRPs are identical within the cluster.

KW - Functional pocket

KW - MHC

KW - Peptide binding

UR - https://www.scopus.com/pages/publications/0038345154

U2 - 10.1016/S0198-8859(03)00078-8

DO - 10.1016/S0198-8859(03)00078-8

M3 - Article

C2 - 12826374

AN - SCOPUS:0038345154

SN - 0198-8859

VL - 64

SP - 718

EP - 728

JO - Human Immunology

JF - Human Immunology

IS - 7

ER -

Compression of functional space in HLA-A sequence diversity

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this