Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide.
To investigate the role of an anchoring pocket in allele-specific peptide presentation by a major histocompatibility complex class I molecule, we "transplanted" a B pocket from HLA-A*0201 into HLA-B*2705 by site-directed mutagenesis. The resulting protein, designated B27.A2B, binds a diffe...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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1993
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| _version_ | 1826269542488211456 |
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| author | Colbert, R Rowland-Jones, S Mcmichael, A Frelinger, J |
| author_facet | Colbert, R Rowland-Jones, S Mcmichael, A Frelinger, J |
| author_sort | Colbert, R |
| collection | OXFORD |
| description | To investigate the role of an anchoring pocket in allele-specific peptide presentation by a major histocompatibility complex class I molecule, we "transplanted" a B pocket from HLA-A*0201 into HLA-B*2705 by site-directed mutagenesis. The resulting protein, designated B27.A2B, binds a different set of endogenous peptides than B*2705 as evidenced by complete loss of allorecognition as well as restored expression in the antigen processing-defective mutant cell line T2. B27.A2B also fails to present an HLA-B27-restricted influenza virus peptide [nucleoprotein (383-391)] to cytotoxic T lymphocytes (CTLs). However, substitution of leucine, the predominant P2 anchor residue in A*0201-restricted peptides, for arginine, the P2 anchor in nucleoprotein-(383-391) and other B*2705-restricted peptides, restores recognition of B27.A2B by the same B*2705-restricted peptide-specific CTLs. These results demonstrate that a dominant polymorphic pocket in a class I molecule, through interaction with the anchor residue of an antigenic peptide, can distinguish among peptides differing by only a single amino acid and thus determine the allelic specificity of peptide presentation. |
| first_indexed | 2024-03-06T21:26:41Z |
| format | Journal article |
| id | oxford-uuid:43541a53-6b00-4001-8ebf-18383921f4b7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:26:41Z |
| publishDate | 1993 |
| record_format | dspace |
| spelling | oxford-uuid:43541a53-6b00-4001-8ebf-18383921f4b72022-03-26T14:54:49ZAllele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:43541a53-6b00-4001-8ebf-18383921f4b7EnglishSymplectic Elements at Oxford1993Colbert, RRowland-Jones, SMcmichael, AFrelinger, JTo investigate the role of an anchoring pocket in allele-specific peptide presentation by a major histocompatibility complex class I molecule, we "transplanted" a B pocket from HLA-A*0201 into HLA-B*2705 by site-directed mutagenesis. The resulting protein, designated B27.A2B, binds a different set of endogenous peptides than B*2705 as evidenced by complete loss of allorecognition as well as restored expression in the antigen processing-defective mutant cell line T2. B27.A2B also fails to present an HLA-B27-restricted influenza virus peptide [nucleoprotein (383-391)] to cytotoxic T lymphocytes (CTLs). However, substitution of leucine, the predominant P2 anchor residue in A*0201-restricted peptides, for arginine, the P2 anchor in nucleoprotein-(383-391) and other B*2705-restricted peptides, restores recognition of B27.A2B by the same B*2705-restricted peptide-specific CTLs. These results demonstrate that a dominant polymorphic pocket in a class I molecule, through interaction with the anchor residue of an antigenic peptide, can distinguish among peptides differing by only a single amino acid and thus determine the allelic specificity of peptide presentation. |
| spellingShingle | Colbert, R Rowland-Jones, S Mcmichael, A Frelinger, J Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide. |
| title | Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide. |
| title_full | Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide. |
| title_fullStr | Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide. |
| title_full_unstemmed | Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide. |
| title_short | Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide. |
| title_sort | allele specific b pocket transplant in class i major histocompatibility complex protein changes requirement for anchor residue at p2 of peptide |
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