Functional analysis of the antigen binding site on the T cell receptor alpha chain
| العنوان: | Functional analysis of the antigen binding site on the T cell receptor alpha chain |
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| المؤلفون: | Anjana Rao, Shailaja Kasibhatla, Eric A. Nalefski |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 1992. |
| سنة النشر: | 1992 |
| مصطلحات موضوعية: | Macromolecular Substances, Protein Conformation, T-Lymphocytes, Molecular Sequence Data, Immunology, Receptors, Antigen, T-Cell, chemical and pharmacologic phenomena, Transfection, Major histocompatibility complex, Substrate Specificity, Major Histocompatibility Complex, Mice, p-Azobenzenearsonate, Antigen, T-Cell Receptor Alpha Chain, Animals, Immunology and Allergy, Amino Acid Sequence, Peptide sequence, Binding Sites, biology, Antigen processing, T-cell receptor, Histocompatibility Antigens Class II, Articles, MHC restriction, Molecular biology, Clone Cells, Models, Structural, Kinetics, Mutagenesis, Site-Directed, biology.protein, Interleukin-2, Haptens, Alpha chain |
| الوصف: | We have identified residues on a T cell receptor (TCR) alpha chain that are important for interaction with antigen/major histocompatibility complex (MHC). Using site-directed mutagenesis, we modified DNA encoding the postulated antigen/MHC binding loops on the TCR alpha chain expressed by the T cell clone D5, which recognizes p-azobenzenearsonate-conjugated antigens presented by cells bearing I-Ad. These variant TCR alpha chains were expressed in conjunction with the wild-type D5 TCR beta chain on the surface of hybridoma cells, and were tested for the ability to recognize hapten-conjugated antigens presented by I-Ad. Individual amino acid substitutions in each of the three antigen binding loops (alpha 1, alpha 2, alpha 3) of the D5 TCR alpha chain affected antigen recognition, demonstrating that all three loops are important in recognition of antigen/MHC. A subset of the single amino acid substitutions completely eliminated antigen recognition, thus identifying the residues that are particularly important in the recognition of antigenic peptide/MHC by the D5 TCR. Because the wild-type D5 TCR recognizes arsonate and certain structural analogues of arsonate conjugated to a variety of protein antigens, we were able to test whether the TCR substitutions affected the specificity of the D5 TCR for hapten or carrier antigen. One substitution introduced into antigen binding loop alpha 3 markedly altered the pattern of carrier recognition. Together, these results verify the Ig model for the TCR and are consistent with the proposition that residues forming the first and second antigen binding loops of the TCR contact the MHC, while those forming the third loop contact mainly antigenic peptides. |
| تدمد: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.175.6.1553 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3ed5f2f7f10a38672ee5ac23808b3ec https://doi.org/10.1084/jem.175.6.1553 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3ed5f2f7f10a38672ee5ac23808b3ec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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| DOI: | 10.1084/jem.175.6.1553 |