3.2-06 The role of signalling through the cytoplasmic domains of MHC class II molecules in antigen presentation

It has been established that at least some V beta 17+ T cells interact with an endogenous superantigen encoded by the murine retrovirus, Mtv-9. To analyze the role of major histocompatibility complex (MHC) class II molecules in presenting the Mtv-9 encoded superantigen, vSAG-9 to V beta 17+ hybridomas, a panel of nine hybridomas was tested for their ability to respond to A20/2J (H-2d) and LBK (H-2a) cells which had been transfected with the vSAG-9 gene. Whereas some of the hybridomas recognized vSAG-9 exclusively in the context of H-2a, other hybridomas recognized vSAG-9 exclusively in the context of H-2d or in the context of both H-2d and H-2a. These results suggest that: (a) the class II MHC molecule plays a direct role in the recognition of retroviral superantigen by T cells, rather than serving simply as a platform for presentation; and, (b) it is likely that components of the TCR other than V beta are involved in the vSAG-9/TCR/class II interaction.

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Antigen Presentation via MHC Class II Molecules

10.1007/springerreference_31811 ◽

2011 ◽

Keyword(s):

Antigen Presentation ◽

Mhc Class Ii ◽

Class Ii ◽

Mhc Class Ii Molecules

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Deficient Major Histocompatibility Complex Class II Antigen Presentation in a Subset of Hodgkin's Disease Tumor Cells

Blood ◽

10.1182/blood.v92.7.2252 ◽

1998 ◽

Vol 92 (7) ◽

pp. 2252-2259 ◽

Cited By ~ 25

Author(s):

Herbert Bosshart ◽

Ruth F. Jarrett

Keyword(s):

Major Histocompatibility Complex ◽

Antigen Presentation ◽

Tumor Cells ◽

Mhc Class Ii ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Class Ii ◽

Histocompatibility Complex ◽

Class Ii Antigen ◽

Mhc Class Ii Molecules

Abstract Hodgkin's disease is a common malignancy of the lymphoid system. Although the scarce Hodgkin and Reed-Sternberg (HRS) tumor cells in involved tissue synthesize major histocompatibility complex (MHC) class II and costimulatory molecules such as CD40 or CD86, it is unclear whether these tumor cells are operational antigen-presenting cells (APC). We developed an immunofluorescence-based assay to determine the number of MHC class II molecules present on the surface of single living HRS cells. We found that in fresh Hodgkin's disease lymph node biopsies, a subset of HRS cells express a substantial number of surface MHC class II molecules that are occupied by MHC class II–associated invariant chain peptides (CLIP), indicating deficient loading of MHC class II molecules with antigenic peptides. Cultured Hodgkin's disease–derived (HD) cell lines, however, were found to express few MHC class II molecules carrying CLIP peptides on the cell surface and were shown to generate sodium dodecyl sulphate (SDS)-stable MHC class II αβ dimers. In addition to showing deficient MHC class II antigen presentation in a subset of HRS cells, our results show that the widely used HD-cell lines are not ideal in vitro models for the disease. The disruption of MHC class II–restricted antigen presentation in HRS cells could represent a key mechanism by which these tumor cells escape immune surveillance.

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