Conformational Correlates of the Epitopes of Human Myelin Basic Protein Peptide 80–89

Abstract

Different epitopes residing within the decapeptide of residues 80-89 of human myelin basic protein (MBP) exist in the MBP-like material detected in human CSF and urine. In the present study, the structure of human MBP peptide 80-89 was examined by a combination of physical measurements and correlated with its varying immunochemical reaction with three polyclonal antisera. At least two epitopes are present in the decapeptide. Progressive shortening and reduction in net negative charge of MBP peptide 80-89 to form peptides 81-89, 82-89, 83-89, and 84-89 revealed an epitope not present in intact MBP. Circular dichroism and Fourier-transform infrared of these MBP peptides in water demonstrated random structure that was partially changed to beta-structure in the shorter peptides. In methanol, used as a model for a lipid environment, the random structure was diminished and was replaced by alpha-helix and beta-structure, especially in the shorter peptides. The findings indicate that the range of epitopes present in this decapeptide is influenced by conformation, which, unexpectedly, becomes progressively less random as the peptide becomes smaller, especially in a hydrophobic environment. This behavior has implications for the immunochemical detection of small antigens or antibodies to them in tissue extracts or body fluids.

Solution NMR structure of an immunodominant epitope of myelin basic protein

“…In organic and membrane-mimetic conditions (30% TFE and 20 mm DPC, respectively), the spectra clearly indicated an a-helical conformation. These results are consistent with previous CD spectroscopic studies of MBP and MBP fragments [38][39][40] and support the inclusion of loose dihedral angle restraints in the structure calculations of FF 2 in TFE-d 2 and DPC-d 38 (see below).…”

Correlation of clinical features and findings on cranial magnetic resonance imaging with urinary myelin basic protein‐like material in patients with multiple sclerosis

“…The clinical correlation has proved to be far more complex than the direct relationship between disease activity, whatever the cause, and the appearance of elevated levels of CSF MBPLM (14,16). The solution of technical requirements for the urine assay, the need to define the specific epitopes involved 1231, awareness of the crucial dependence of conformation on the immunochemical detection of MBPLM [28), and the correction of the sequence in the peptide region of MBP residues 80 to 89 131) were requisite steps to make this investigation possible. Problems in defining the demands on this assay have led to considerable problems in all laboratories addressing this issue [24}.…”

Myelin basic protein—diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis

“…3), is the minimal B cell epitope of MBP, and is also an important T cell recognition site (Whitaker et al, 1990;Warren et al, 1995). This region of the protein is highly conserved in sequence (Fig.…”