Analysis of the mutant HLA-A*0201 heavy chain H74L

Impaired TAP- dependent peptide loading

Rebecca R P Caley, Amy L. Peace-Brewer, Masanori Matsui, Jeffrey A Frelinger

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A mutation of the HLA-A*0201 heavy chain at position 74 from histidine to leucine (H74L) resulted in a molecule with an interesting phenotype. H74L- expressing targets were recognized by peptide-specific HLA-A*0201-restricted cytotoxic T lymphocytes at lower peptide concentrations than wild type HLA- A*0201. H74L's improved ability to sensitize cells for lysis was due to its enhanced capability to bind exogenous peptide. Furthermore, this phenotype of improved exogenous binding and functional recognition was not peptide- specific, in contrast, the H74L molecule failed to present the HIV-1 HLA-A2- restricted pol peptide when expressed and processed endogenously. The inability to bind endogenous pol could be rescued by preceding the pol peptide with a signal sequence. The defect affecting endogenous presentation, therefore, appeared to be limited to the TAP-dependent pathway. Surprisingly, the H74L heavy chain was able to enter the defined MHC class I pathway and associate with β2M, calreticulin, tapasin, and TAP. Despite the presence of the H74L heavy chain at the TAP complex, H74L was functionally inefficient at loading TAP-dependent peptides. H74L may help elucidate further steps in the process of loading TAP-dependent peptides into the class I cleft.

Original languageEnglish (US)
Pages (from-to)743-754
Number of pages12
JournalHuman Immunology
Volume60
Issue number9
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

trypsinogen activation peptide
Peptides
Calreticulin
Phenotype
HLA-A2 Antigen
Cytotoxic T-Lymphocytes
Protein Sorting Signals
Histidine
Leucine
HLA-A*02:01 antigen
HIV-1

Keywords

  • Antigen binding
  • Antigen presentation
  • MHC
  • Transporters

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Analysis of the mutant HLA-A*0201 heavy chain H74L : Impaired TAP- dependent peptide loading. / Caley, Rebecca R P; Peace-Brewer, Amy L.; Matsui, Masanori; Frelinger, Jeffrey A.

In: Human Immunology, Vol. 60, No. 9, 1999, p. 743-754.

Research output: Contribution to journalArticle

Caley, Rebecca R P ; Peace-Brewer, Amy L. ; Matsui, Masanori ; Frelinger, Jeffrey A. / Analysis of the mutant HLA-A*0201 heavy chain H74L : Impaired TAP- dependent peptide loading. In: Human Immunology. 1999 ; Vol. 60, No. 9. pp. 743-754.
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