MHC class II deficiency: definition of a new complementation group

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• MHC class II deficiency is a severe primary immunodeficiency.
• It is genetically heterogeneous, with defects in regulatory factors causing absent MHC class II gene expression.
• Existing patient cell lines fall into complementation groups A, B, and C, with group D previously represented by a single cell line.

Purpose of the Study:

• To investigate the genetic basis of MHC class II deficiency in patients not assigned to known complementation groups.
• To identify the molecular defect in the previously described group D cell line (6.1.6).
• To define new complementation groups for MHC class II deficiency.

Main Methods:

• Direct complementation experiments using cell lines from MHC class II deficiency patients.
• Mutation analysis of candidate genes, including the recently cloned RFXAP gene.
• Characterization of the molecular defect in the 6.1.6 cell line.

Main Results:

• The molecular defect in the 6.1.6 cell line was identified as a mutation in the RFXAP gene.
• Complementation experiments revealed that several previously unassigned patient cell lines also harbor mutations in the RFXAP gene.
• This defines a new complementation group (group D) for MHC class II deficiency.

Conclusions:

• Mutations in the RFXAP gene are a cause of MHC class II deficiency.
• A previously unrecognized complementation group for MHC class II deficiency is defined by defects in the RFXAP gene.
• This finding expands the understanding of the genetic heterogeneity of MHC class II deficiency.