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 journalArticlepeer-review

2 Scopus citations


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
Issue number9
StatePublished - Sep 1999


  • Antigen binding
  • Antigen presentation
  • MHC
  • Transporters

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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