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Analyses of t cells in transgenic mice carrying "humanized" mhc and cartilage as a model for rheumatoid arthritis

Objective



Rheumatoid arthritis is genetically associated with the major histocompatibility complex class II region (HLA-DR4) suggesting involvement of T cell mediated autoimmune recognition of joint specific antigens. Only cartilage contain joint-specific proteins. The most widely used model is arthritis induced with type II collagen (CII), The major protein component of cartilage. To understand the role of CII-reactive T-cells a series of precisely designed transgenic mice are available in Lund. This includes mice with human CII instead of mouse CII in cartilage (obtained by crossing human CII transgenic with mouse CII deleted mice) and mice with functional expression of human DR4. They have already defined the epitope in human CII recognised by murine T cells. This epitope can be recognised in its glycosylated form. Partially tolerised T-cells against this epitope develop in mice expressing the epitope in cartilage and the mice will eventually develop arthritis. I will analyse the precise nature of the tolerance. The methods I will use include T-cell cloning, cytokine analysis and TCR sequencing.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

LUND UNIVERSITY
Address
39,Soelvegatan 19 , Bmc:l11
221 84 Lund
Sweden

Participants (1)

Not available
France