LICOS, a primordial costimulatory ligand?
In mammals, the classical B7 molecules expressed on antigen-presenting cells, B7-1 (CD80) and B7-2 (CD86), bind the structurally related glycoproteins CD28 and CTLA-4 (CD152), generating costimulatory signals that regulate the activation state of T cells. A recently identified human CD28-like protei...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2000
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| _version_ | 1826278740778287104 |
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| author | Brodie, D Collins, A Iaboni, A Fennelly, J Sparks, L Xu, X Van Der Merwe, P Davis, S |
| author_facet | Brodie, D Collins, A Iaboni, A Fennelly, J Sparks, L Xu, X Van Der Merwe, P Davis, S |
| author_sort | Brodie, D |
| collection | OXFORD |
| description | In mammals, the classical B7 molecules expressed on antigen-presenting cells, B7-1 (CD80) and B7-2 (CD86), bind the structurally related glycoproteins CD28 and CTLA-4 (CD152), generating costimulatory signals that regulate the activation state of T cells. A recently identified human CD28-like protein, ICOS, also induces costimulatory signals in T cells when crosslinked with antibodies, but it is unclear whether ICOS is part of a B7-mediated regulatory pathway of previously unsuspected complexity, or whether it functions independently and in parallel. Here, we report that, rather than binding B7-1 or B7-2, ICOS binds a new B7-related molecule of previously unknown function that we call LICOS (for ligand of ICOS). At 37 degrees C, LICOS binds only to ICOS but, at lower, non-physiological temperatures, it also binds weakly to CD28 and CTLA-4. Sequence comparisons suggest that LICOS is the homologue of a molecule expressed by avian macrophages and of a murine protein whose expression is induced in non-lymphoid organs by tumour necrosis factor alpha (TNFalpha). Our results define the components of a distinct and novel costimulatory pathway and raise the possibility that LICOS, rather than B7-1 or B7-2, is the contemporary homologue of a primordial vertebrate costimulatory ligand. |
| first_indexed | 2024-03-06T23:48:28Z |
| format | Journal article |
| id | oxford-uuid:71c7c327-f184-4a77-bfd7-ede3872d596e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:48:28Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:71c7c327-f184-4a77-bfd7-ede3872d596e2022-03-26T19:45:43ZLICOS, a primordial costimulatory ligand?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:71c7c327-f184-4a77-bfd7-ede3872d596eEnglishSymplectic Elements at Oxford2000Brodie, DCollins, AIaboni, AFennelly, JSparks, LXu, XVan Der Merwe, PDavis, SIn mammals, the classical B7 molecules expressed on antigen-presenting cells, B7-1 (CD80) and B7-2 (CD86), bind the structurally related glycoproteins CD28 and CTLA-4 (CD152), generating costimulatory signals that regulate the activation state of T cells. A recently identified human CD28-like protein, ICOS, also induces costimulatory signals in T cells when crosslinked with antibodies, but it is unclear whether ICOS is part of a B7-mediated regulatory pathway of previously unsuspected complexity, or whether it functions independently and in parallel. Here, we report that, rather than binding B7-1 or B7-2, ICOS binds a new B7-related molecule of previously unknown function that we call LICOS (for ligand of ICOS). At 37 degrees C, LICOS binds only to ICOS but, at lower, non-physiological temperatures, it also binds weakly to CD28 and CTLA-4. Sequence comparisons suggest that LICOS is the homologue of a molecule expressed by avian macrophages and of a murine protein whose expression is induced in non-lymphoid organs by tumour necrosis factor alpha (TNFalpha). Our results define the components of a distinct and novel costimulatory pathway and raise the possibility that LICOS, rather than B7-1 or B7-2, is the contemporary homologue of a primordial vertebrate costimulatory ligand. |
| spellingShingle | Brodie, D Collins, A Iaboni, A Fennelly, J Sparks, L Xu, X Van Der Merwe, P Davis, S LICOS, a primordial costimulatory ligand? |
| title | LICOS, a primordial costimulatory ligand? |
| title_full | LICOS, a primordial costimulatory ligand? |
| title_fullStr | LICOS, a primordial costimulatory ligand? |
| title_full_unstemmed | LICOS, a primordial costimulatory ligand? |
| title_short | LICOS, a primordial costimulatory ligand? |
| title_sort | licos a primordial costimulatory ligand |
| work_keys_str_mv | AT brodied licosaprimordialcostimulatoryligand AT collinsa licosaprimordialcostimulatoryligand AT iabonia licosaprimordialcostimulatoryligand AT fennellyj licosaprimordialcostimulatoryligand AT sparksl licosaprimordialcostimulatoryligand AT xux licosaprimordialcostimulatoryligand AT vandermerwep licosaprimordialcostimulatoryligand AT daviss licosaprimordialcostimulatoryligand |