Recognition of HLA-DR1/DRB1*0101 molecules presenting HLA-A2 derived peptides by a human recombinant antibody, Fab-5 A1

Eur J Immunogenet. 1998 Oct;25(5):339-47. doi: 10.1046/j.1365-2370.1998.00120.x.

Abstract

MHC molecules present peptides in their binding groove to T-cell receptors inducing proliferation or cytotoxicity of alloreactive T cells. A previously generated human monoclonal antibody (mAb) UL-5 A1, recognizing a conformational epitope formed by HLA DR1/DRB1*0101 molecules and HLA-A2 derived peptides, demonstrates T-cell-like recognition of the peptide/MHC complex (PMC). To study the genes of the antigen binding region, the nucleotide sequences of the rearranged genes in the variable regions of UL-5 A1 were determined and the V-gene usage (VH3, V lambda 2) was identified by comparison with published germlines. The genes encoding heavy (Fd) and light (L) chains of UL-5 A1 were linked and expressed in a bacterial system. Specificity of the recombinant Fab-5 A1 was determined with HLA-typed LCLs by flow cytometric analysis. As demonstrated in competitive inhibition assays, UL-5 A1 and Fab-5 A1 recognize the same PMC epitope on HLA-A2+, -DR1/DRB1*0101+ typed LCLs. Additionally, mAb UL-5 A1 and Fab-5 A1 both recognize HLA-A2-, -DR1/DRB1*0101+ LCLs exogenously loaded with HLA-A2 peptides (105-117, 103-117). UL-5 A1-like antibodies against peptide/MHC complexes could prove valuable tools for research on T-cell recognition and MHC function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology
  • Antigen Presentation / immunology*
  • Base Sequence
  • Binding, Competitive
  • Cell Line, Transformed
  • DNA, Complementary
  • Flow Cytometry
  • HLA-A2 Antigen / immunology*
  • HLA-DR Antigens / immunology*
  • HLA-DR1 Antigen / immunology*
  • HLA-DRB1 Chains
  • Humans
  • Immunoglobulin Fab Fragments / immunology
  • Molecular Sequence Data
  • Peptides / immunology
  • Recombinant Proteins / immunology
  • Sequence Analysis

Substances

  • Antibodies, Monoclonal
  • DNA, Complementary
  • HLA-A2 Antigen
  • HLA-DR Antigens
  • HLA-DR1 Antigen
  • HLA-DRB1 Chains
  • Immunoglobulin Fab Fragments
  • Peptides
  • Recombinant Proteins

Associated data

  • GENBANK/AF032350
  • GENBANK/AF032351