Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity.
The role of processing in antigen (Ag) presentation and T cell activation in experimental allergic encephalomyelitis (EAE) was evaluated in wild-type mice, mice that selectively express either Ii p31 or p41, and mice completely deficient in Ii or H-2M. We demonstrate that processing of myelin oligod...
| Hauptverfasser: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Sprache: | English |
| Veröffentlicht: |
2001
|
| _version_ | 1826285411540926464 |
|---|---|
| author | Slavin, A Soos, J Stuve, O Patarroyo, J Weiner, H Fontana, A Bikoff, E Zamvil, S |
| author_facet | Slavin, A Soos, J Stuve, O Patarroyo, J Weiner, H Fontana, A Bikoff, E Zamvil, S |
| author_sort | Slavin, A |
| collection | OXFORD |
| description | The role of processing in antigen (Ag) presentation and T cell activation in experimental allergic encephalomyelitis (EAE) was evaluated in wild-type mice, mice that selectively express either Ii p31 or p41, and mice completely deficient in Ii or H-2M. We demonstrate that processing of myelin oligodendrocyte glycoprotein (MOG) is required for presentation of the dominant encephalitogenic MOG epitope, p35-55. Ii p31- and p41-expressing mice developed EAE with similar incidence to wild-type mice, although p41 mice had a more severe course. Ag-presenting cells (APCs) from Ii- or H-2M-deficient mice could present p35-55, but not MOG, demonstrating that these APCs could not process native MOG. Ii- and H-2M-deficient mice were not susceptible to EAE by immunization with p35-55 or MOG or by adoptive transfer of encephalitogenic T cells. However, CD4+ T cells from p35-55-immunized H-2M-deficient mice proliferated, secreted IFN-gamma, and transferred EAE to wild-type, but not H-2M-deficient, mice. Thus, EAE resistance in H-2M-deficient mice is not due to an inability of APCs to present p35-55, or an intrinsic defect in the encephalitogenic T cell repertoire, but reflects a defect in APC function. Our results indicate that processing is required for initial Ag presentation and CNS T cell activation and suggest that autopathogenic peptides of CNS autoantigen may not be readily available for presentation without processing. |
| first_indexed | 2024-03-07T01:28:26Z |
| format | Journal article |
| id | oxford-uuid:92c0e7b2-fe1f-4122-81c1-d6123b09591c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:28:26Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:92c0e7b2-fe1f-4122-81c1-d6123b09591c2022-03-26T23:27:50ZRequirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:92c0e7b2-fe1f-4122-81c1-d6123b09591cEnglishSymplectic Elements at Oxford2001Slavin, ASoos, JStuve, OPatarroyo, JWeiner, HFontana, ABikoff, EZamvil, SThe role of processing in antigen (Ag) presentation and T cell activation in experimental allergic encephalomyelitis (EAE) was evaluated in wild-type mice, mice that selectively express either Ii p31 or p41, and mice completely deficient in Ii or H-2M. We demonstrate that processing of myelin oligodendrocyte glycoprotein (MOG) is required for presentation of the dominant encephalitogenic MOG epitope, p35-55. Ii p31- and p41-expressing mice developed EAE with similar incidence to wild-type mice, although p41 mice had a more severe course. Ag-presenting cells (APCs) from Ii- or H-2M-deficient mice could present p35-55, but not MOG, demonstrating that these APCs could not process native MOG. Ii- and H-2M-deficient mice were not susceptible to EAE by immunization with p35-55 or MOG or by adoptive transfer of encephalitogenic T cells. However, CD4+ T cells from p35-55-immunized H-2M-deficient mice proliferated, secreted IFN-gamma, and transferred EAE to wild-type, but not H-2M-deficient, mice. Thus, EAE resistance in H-2M-deficient mice is not due to an inability of APCs to present p35-55, or an intrinsic defect in the encephalitogenic T cell repertoire, but reflects a defect in APC function. Our results indicate that processing is required for initial Ag presentation and CNS T cell activation and suggest that autopathogenic peptides of CNS autoantigen may not be readily available for presentation without processing. |
| spellingShingle | Slavin, A Soos, J Stuve, O Patarroyo, J Weiner, H Fontana, A Bikoff, E Zamvil, S Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. |
| title | Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. |
| title_full | Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. |
| title_fullStr | Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. |
| title_full_unstemmed | Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. |
| title_short | Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. |
| title_sort | requirement for endocytic antigen processing and influence of invariant chain and h 2m deficiencies in cns autoimmunity |
| work_keys_str_mv | AT slavina requirementforendocyticantigenprocessingandinfluenceofinvariantchainandh2mdeficienciesincnsautoimmunity AT soosj requirementforendocyticantigenprocessingandinfluenceofinvariantchainandh2mdeficienciesincnsautoimmunity AT stuveo requirementforendocyticantigenprocessingandinfluenceofinvariantchainandh2mdeficienciesincnsautoimmunity AT patarroyoj requirementforendocyticantigenprocessingandinfluenceofinvariantchainandh2mdeficienciesincnsautoimmunity AT weinerh requirementforendocyticantigenprocessingandinfluenceofinvariantchainandh2mdeficienciesincnsautoimmunity AT fontanaa requirementforendocyticantigenprocessingandinfluenceofinvariantchainandh2mdeficienciesincnsautoimmunity AT bikoffe requirementforendocyticantigenprocessingandinfluenceofinvariantchainandh2mdeficienciesincnsautoimmunity AT zamvils requirementforendocyticantigenprocessingandinfluenceofinvariantchainandh2mdeficienciesincnsautoimmunity |