Epitopes susceptibility

Rossman MD, Stubbs J, Lee CW, et al. Human leukocyte antigen class II amino acid epitopes susceptibility and progression markers for beryllium hypersensitivity. Am J Respir Crit Care Med 2002 165(6) 788-794. 

To study the role of lysine residues in susceptibility to formalin fixation, the amino acid composition of immunoreactive peptides (to various monoclonal antibodies) was studied. Each peptide was evaluated to determine if immu-noreactivity was lost after formalin fixation. Formalin sensitivity was correlated with the peptides amino acid composition. The first step in the method is biopanning from a peptide combinatorial library with a monoclonal antibody. The peptides that bind to the antibody were tested for their sensitivity to formalin fixation. Some peptides remain immunoreactive whereas others do not. The peptides were then sequenced to look for differences between those that were sensitive to formaldehyde versus those that were not. The goal was to find whether there is a particular amino acid that is present in formalin-sensitive epitopes but absent in formalin-resistant epitopes, or vice versa. An advantage of this approach is that it is open-ended, without excluding any amino acids. 

Gregersen, P. K., Silver, J., and Winchester, R.J. (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis and Rheumatism. 30, 1205-1213. 

Another means of tolerance is based on molecular mimicry whereby a native protein has a similar epitope to the antigen, so the immune system is tolerant to this in most individuals. The suggestion is that the patients who are susceptible have some variation in this native protein so that tolerance has not been acquired. 

HiU M, Beeson D, Moss P, Jacobson L, Bond A, Corlett L, Newsom-Davis J, Vincent A, WUlcox N. Early-onset myasthenia gravis a recurring T-cell epitope in the adult-specific acetylcholine receptor epsilon subunit presented by the susceptibility allele HLA-DR52a. Ann Neurol 1999 45(2) 224-31. 

In the previous section we discussed the presence of oligosaccharide and protein blood group substances that cause susceptibility to certain pathogens. In this section we discuss an infectious agent that contains a common antigenic epitope with the host and that elicits antibodies that cause a disease. Guillain—Barre syndrome (GBS) is one such disease. GBS is an acute inflammatory neuropathy with progressive weakness in both arms... 

Rheumatoid arthritis (RA) In most Caucasian populations, susceptibility to (or severity of) RA is due to a closely related set of polymorphic sequences (the shared epitope ) on several different HLA-DRB1 alleles, especially certain subtypes of the DR4 and DR1 allelic families (Gregersen et al., 1987 Nepom, 1998). Some genetically distant populations exhibit a different association (e.g. HLA-DR9 in Native Americans, HLA-DR3 in RA patients from Finland) (Hakala et al., 1997). Ferucci et al. (2005) found genetic susceptibility to the development of RA in the American Indian/Alaskan Native populations at least partially associated with different HLA alleles, such as HLA-DRB1 1402, among other possible genetic factors yet elucidated. 

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