T-cell clones identify three distinct epitopes associated with HLA-Dw14.
Alloreactive T-cell clones were used to study allodeterminants associated with the HLA-DR1, -DR4, and -DRw14 allelic families. Three clones derived by priming against the DR4,Dw14 alloantigen were tested against a panel of HLA-D homozygous B-cell lines and homozygous and heterozygous peripheral blood lymphocytes. Each clone was blocked by monoclonal antibodies specific for HLA-DR, but not HLA-DQ or -DP, molecules, and each showed a unique pattern of allorecognition when tested against the cell panel. Clone 14B appeared to recognize a specific sequence, termed L67-A74, comprised of amino acids in the third hypervariable region of the alpha-helix of the DR beta 1 molecule, and expressed on certain DR1-, DR4-, and DRw14-positive cells. Clone EMO25 recognized the same L67-A74 sequence, but only when expressed on DR4-positive cells, suggesting a role for residues in the first and second hypervariable regions of DR4-positive DR beta 1 molecules in T-cell recognition. Clone EM036 also recognized the L67-A74 sequence, but only when expressed on DR4,Dw14.1-positive cells, implicating residues at positions 57 and 86 of the alpha-helix in T-cell recognition. These results demonstrate the range of specific T-cell responses that are possible against alloepitopes expressed by a single class II allele (Dw14), and are an indication of the diverse regions of the class II molecule that can contribute to allorecognition sites.
Mickelson
E M
EM
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Masewicz
S
S
Smith
A
A
Petersdorf
E
E
Nepom
G T
GT
Martin
P J
PJ
Hansen
J A
JA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology*; D015798:HLA-DR1 Antigen / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006681:HLA-D Antigens; D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; C050381:HLA-Dw14 antigen