Virtual models of the HLA class I antigen processing pathway

Nikolai Petrovsky, Vladimir Brusic

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Antigen recognition by cytotoxic CD8 T cells is dependent upon a number of critical steps in MHC class I antigen processing including proteosomal cleavage, TAP transport into the endoplasmic reticulum, and MHC class I binding. Based on extensive experimental data relating to each of these steps there is now the capacity to model individual antigen processing steps with a high degree of accuracy. This paper demonstrates the potential to bring together models of individual antigen processing steps, for example proteosome cleavage, TAP transport, and MHC binding, to build highly informative models of functional pathways. In particular, we demonstrate how an artificial neural network model of TAP transport was used to mine a HLA-binding database so as to identify HLA-binding peptides transported by TAP. This integrated model of antigen processing provided the unique insight that HLA class I alleles apparently constitute two separate classes: those that are TAP-efficient for peptide loading (HLA-B27, -A3, and -A24) and those that are TAP-inefficient (HLA-A2, -B7, and -B8). Hence, using this integrated model we were able to generate novel hypotheses regarding antigen processing, and these hypotheses are now capable of being tested experimentally. This model confirms the feasibility of constructing a virtual immune system, whereby each additional step in antigen processing is incorporated into a single modular model. Accurate models of antigen processing have implications for the study of basic immunology as well as for the design of peptide-based vaccines and other immunotherapies.

Original languageEnglish
Pages (from-to)429-435
Number of pages7
JournalMethods
Volume34
Issue number4
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

Fingerprint

Histocompatibility Antigens Class I
Antigen Presentation
HLA Antigens
trypsinogen activation peptide
Processing
Antigens
HLA-A3 Antigen
HLA-B7 Antigen
User-Computer Interface
HLA-A2 Antigen
HLA-B27 Antigen
Subunit Vaccines
Neural Networks (Computer)
Immunology
Allergy and Immunology
Peptides
Endoplasmic Reticulum
Immunotherapy
T-cells
Immune system

Keywords

  • Artificial neural networks
  • Human leukocyte antigen
  • Major histocompatibility complex
  • Transporter associated with antigen processing

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Virtual models of the HLA class I antigen processing pathway. / Petrovsky, Nikolai; Brusic, Vladimir.

In: Methods, Vol. 34, No. 4, 12.2004, p. 429-435.

Research output: Contribution to journalArticle

Petrovsky, Nikolai ; Brusic, Vladimir. / Virtual models of the HLA class I antigen processing pathway. In: Methods. 2004 ; Vol. 34, No. 4. pp. 429-435.
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