Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes.
We have synthesized a recombinant gene encoding a single-chain HLA-A2/beta 2-microglobulin (beta 2m) molecule by linking beta 2m through its carboxyl terminus via a short peptide spacer to HLA-A2 (A*0201). This gene has been expressed in the beta 2m-deficient colorectal tumor cell line DLD-1. Transf...
Main Authors: | , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
1996
|
_version_ | 1797062239853740032 |
---|---|
author | Toshitani, K Braud, V Browning, M Murray, N Mcmichael, A Bodmer, W |
author_facet | Toshitani, K Braud, V Browning, M Murray, N Mcmichael, A Bodmer, W |
author_sort | Toshitani, K |
collection | OXFORD |
description | We have synthesized a recombinant gene encoding a single-chain HLA-A2/beta 2-microglobulin (beta 2m) molecule by linking beta 2m through its carboxyl terminus via a short peptide spacer to HLA-A2 (A*0201). This gene has been expressed in the beta 2m-deficient colorectal tumor cell line DLD-1. Transfection of this cell with the single-chain construct was associated with conformationally correct cell surface expression of a class I molecule of appropriate molecular mass. The single-chain HLA class I molecule presented either exogenously added peptide or (after interferon-gamma treatment) endogenously processed antigen to an influenza A matrix-specific, HLA-A2-restricted cytotoxic T-lymphocyte line. The need for interferon gamma for the processing and presentation of endogenous antigen suggests that DLD-1 has an antigen-processing defect that can be up-regulated, a feature that may be found in other carcinomas. Our data indicate that single-chain HLA class I constructs can form functional class I molecules capable of presenting endogenously processed antigens. Such molecules should be of use for functional studies, as well as providing potential anticancer immunotherapeutic agents or vaccines. |
first_indexed | 2024-03-06T20:42:41Z |
format | Journal article |
id | oxford-uuid:34c8586e-13ef-4d86-b505-a129c9611f81 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T20:42:41Z |
publishDate | 1996 |
record_format | dspace |
spelling | oxford-uuid:34c8586e-13ef-4d86-b505-a129c9611f812022-03-26T13:28:14ZExpression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:34c8586e-13ef-4d86-b505-a129c9611f81EnglishSymplectic Elements at Oxford1996Toshitani, KBraud, VBrowning, MMurray, NMcmichael, ABodmer, WWe have synthesized a recombinant gene encoding a single-chain HLA-A2/beta 2-microglobulin (beta 2m) molecule by linking beta 2m through its carboxyl terminus via a short peptide spacer to HLA-A2 (A*0201). This gene has been expressed in the beta 2m-deficient colorectal tumor cell line DLD-1. Transfection of this cell with the single-chain construct was associated with conformationally correct cell surface expression of a class I molecule of appropriate molecular mass. The single-chain HLA class I molecule presented either exogenously added peptide or (after interferon-gamma treatment) endogenously processed antigen to an influenza A matrix-specific, HLA-A2-restricted cytotoxic T-lymphocyte line. The need for interferon gamma for the processing and presentation of endogenous antigen suggests that DLD-1 has an antigen-processing defect that can be up-regulated, a feature that may be found in other carcinomas. Our data indicate that single-chain HLA class I constructs can form functional class I molecules capable of presenting endogenously processed antigens. Such molecules should be of use for functional studies, as well as providing potential anticancer immunotherapeutic agents or vaccines. |
spellingShingle | Toshitani, K Braud, V Browning, M Murray, N Mcmichael, A Bodmer, W Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes. |
title | Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes. |
title_full | Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes. |
title_fullStr | Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes. |
title_full_unstemmed | Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes. |
title_short | Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes. |
title_sort | expression of a single chain hla class i molecule in a human cell line presentation of exogenous peptide and processed antigen to cytotoxic t lymphocytes |
work_keys_str_mv | AT toshitanik expressionofasinglechainhlaclassimoleculeinahumancelllinepresentationofexogenouspeptideandprocessedantigentocytotoxictlymphocytes AT braudv expressionofasinglechainhlaclassimoleculeinahumancelllinepresentationofexogenouspeptideandprocessedantigentocytotoxictlymphocytes AT browningm expressionofasinglechainhlaclassimoleculeinahumancelllinepresentationofexogenouspeptideandprocessedantigentocytotoxictlymphocytes AT murrayn expressionofasinglechainhlaclassimoleculeinahumancelllinepresentationofexogenouspeptideandprocessedantigentocytotoxictlymphocytes AT mcmichaela expressionofasinglechainhlaclassimoleculeinahumancelllinepresentationofexogenouspeptideandprocessedantigentocytotoxictlymphocytes AT bodmerw expressionofasinglechainhlaclassimoleculeinahumancelllinepresentationofexogenouspeptideandprocessedantigentocytotoxictlymphocytes |