Re: MHC reponses to erythrocyte antigens vs protein antigens

Hi Sarah,

Thanks for your questions.

Specificities of mouse MHC (H-2) are identified by a number. Since laboratory mice are inbred, each strain is homozygous and has a unique haplotype. The MHC haplotype in these strains is designated by a 'small' letter (a, b, d, k, q, s, etc.); for example, the MHC haplotype of Balb/c mice is H2d. For even more information see :
http://www.biolegend.com/media_assets/support_resource/BioLegend_Mouse_Alloantigens.pdf

Both sheep erythrocytes and hen egg lysozyme (HEL) are protein antigens. They are both presented by MHC II if they are encountered by an antigen presenting cell such as a dendritic cell or a B cell. HEL will be endocytosed, cleaved and presented directly by the MHC II while sheep erythrocytes will have to be phagocytosed, destroyed in the lysosome and their protein antigens will then be cleaved and presented by the MHC II.

MHC I presents antigens that are synthesized by the cell itself, and is mostly important to identify cells that are infected by viruses or intracellular parasites.

Of course, sheep erythrocytes contain much more protein antigens than the single protein that is hen egg lysozyme. Furthermore, minor histocompatibility antigens found on the sheep erythrocyte will induce a strong xenogeneic immune response as the immune system of the mouse will immediately recognize them as "foreign" and respond accordingly. The immune system of the mouse will have multiple antigens to use to initiate a strong immune response. Conversely, for the hen egg lysozyme protein, the immune system of the mouse will have only one protein from which to derive peptides to be presented to CD4 T cells via MHC II. Hence, some MHC haplotypes could have a harder time to present an immunogenic peptide of HEL. This explains why all mice strains will respond against a mixture of foreign antigens (sheep erythrocytes) while only some will respond against a single antigen (HEL).

Antibody responses to HEL or sheep erythrocytes are T-dependent, will induce an isotype switch and will occur mostly through IgGs.

I hope this answered your questions.

Michel Ouellet, Ph.D.