TY - JOUR
T1 - A new type of metal recognition by human T cells
T2 - Contact residues for peptide-independent bridging of T cell receptor and major histocompatibility complex by nickel
AU - Gamerdinger, Katharina
AU - Moulon, Corinne
AU - Karp, David R.
AU - Van Bergen, Jeroen
AU - Koning, Frits
AU - Wild, Doris
AU - Pflugfelder, Ulrike
AU - Weltzien, Hans Ulrich
PY - 2003/5/19
Y1 - 2003/5/19
N2 - In spite of high frequencies of metal allergies, the structural basis for major histocompatibility complex (MHC)-restricted metal recognition is among the unanswered questions in the field of T cell activation. For the human T cell clone SE9, we have identified potential Ni contact sites in the T cell receptor (TCR) and the restricting human histocompatibility leukocyte antigen (HLA)-DR structure. The specificity of this HLA-DR-promiscuous VA22/VB17+ TCR is primarily harbored in its α chain. Ni reactivity is neither dependent on protein processing in antigen-presenting cells nor affected by the nature of HLA-DR-associated peptides. However, SE9 activation by Ni crucially depends on Tyr29 in CDR1α, an N-nucleotide-encoded Tyr94 in CDR3α, and a conserved His81 in the HLA-DR β chain. These data indicate that labile, nonactivating complexes between the SE9 TCR and most HLA-DR/peptide conjugates might supply sterically optimized coordination sites for Ni ions, three of which were identified in this study. In such complexes Ni may effectively bridge the TCR α chain to His81 of most DR molecules. Thus, in analogy to superantigens, Ni may directly link TCR and MHC in a peptide-independent manner. However, unlike superantigens, Ni requires idiotypic, i.e., CDR3α-determined TCR amino acids. This new type of TCR-MHC linkage might explain the high frequency of Ni-reactive T cells in the human population.
AB - In spite of high frequencies of metal allergies, the structural basis for major histocompatibility complex (MHC)-restricted metal recognition is among the unanswered questions in the field of T cell activation. For the human T cell clone SE9, we have identified potential Ni contact sites in the T cell receptor (TCR) and the restricting human histocompatibility leukocyte antigen (HLA)-DR structure. The specificity of this HLA-DR-promiscuous VA22/VB17+ TCR is primarily harbored in its α chain. Ni reactivity is neither dependent on protein processing in antigen-presenting cells nor affected by the nature of HLA-DR-associated peptides. However, SE9 activation by Ni crucially depends on Tyr29 in CDR1α, an N-nucleotide-encoded Tyr94 in CDR3α, and a conserved His81 in the HLA-DR β chain. These data indicate that labile, nonactivating complexes between the SE9 TCR and most HLA-DR/peptide conjugates might supply sterically optimized coordination sites for Ni ions, three of which were identified in this study. In such complexes Ni may effectively bridge the TCR α chain to His81 of most DR molecules. Thus, in analogy to superantigens, Ni may directly link TCR and MHC in a peptide-independent manner. However, unlike superantigens, Ni requires idiotypic, i.e., CDR3α-determined TCR amino acids. This new type of TCR-MHC linkage might explain the high frequency of Ni-reactive T cells in the human population.
KW - Antigen presentation
KW - Hapten
KW - Hypersensitivity
KW - Mutation
KW - T cell receptor
UR - http://www.scopus.com/inward/record.url?scp=0037515534&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037515534&partnerID=8YFLogxK
U2 - 10.1084/jem.20030121
DO - 10.1084/jem.20030121
M3 - Article
C2 - 12756270
AN - SCOPUS:0037515534
SN - 0022-1007
VL - 197
SP - 1345
EP - 1353
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -