A single amino acid substitution in the human histocompatibility leukocyte antigen DR3 beta chain selectively alters antigen presentation.
Activation of T lymphocytes by immunogenic peptides bound to HLA molecules is a central event in the generation of an immune response. To determine the sites on HLA molecules involved in this process, we isolated mutant EBV-transformed B cell clones that express altered HLA-DR3 molecules. One mutant has lost the ability to stimulate a T cell clone specific for a mycobacterial protein, but retains the ability to stimulate other antigen-specific T cells. The DNA sequence of the complete DR alpha and beta coding regions revealed a single nucleotide change resulting in a glutamic acid to lysine substitution at amino acid 9 in the first hypervariable region of the DR beta chain. These results are discussed in relation to a recently proposed model of class II molecule structure.
Mellins
E
E
Department of Pediatrics, University of Washington, Seattle 98195.
Arp
B
B
Ochs
B
B
Erlich
H
H
Pious
D
D
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000502:physiology*; D006684:HLA-DR Antigens / Q000502:physiology*; D015803:HLA-DR3 Antigen; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology
D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen