Influence of amino acid substitutions on antigenicity of immunodominant regions of the HTLV type I envelope surface gylcoprotein: A study using monoclonal antibodies raised against relevant peptides
D. Londos-gagliardi et al., Influence of amino acid substitutions on antigenicity of immunodominant regions of the HTLV type I envelope surface gylcoprotein: A study using monoclonal antibodies raised against relevant peptides, AIDS RES H, 15(10), 1999, pp. 909-920
By the use of sera of human T cell leukemia virus type I (HTVL-I)-infected
individuals it was shown that amino acid substitutions at positions 192 (pr
oline to serine) and 250 (serine to proline) in major immunodominant region
s (175-199 and 239-261) of the surface envelope glycoprotein (gp46) of the
virus may influence the humoral response. Since human sera are polyclonal i
n nature, one cannot readily discriminate between an immunoglobulin-specifi
c recognition and multiple bindings of diverse antibodies. To overcome this
difficulty we generated murine monoclonal antibodies to synthetic peptides
mimicking all or portions of these gp46 regions, The reactivity of some of
these antibodies to synthetic peptides harboring (or not harboring) the pr
eceding amino acid substitutions at position 192 or 250, to denatured gp46
by Western blotting, and to live (variously substituted) HTLV-I-infected ce
lls, combined with blocking experiments with various peptides, allow us to
conclude that the major epitopes (positions 183-191, 190-197, 190-199, and
246-252) in the two immunodominant regions may elicit different antibody re
sponses according to their sequences. It is worth noting that in a reporter
gene inhibition assay, it was found that a neutralizing monoclonal antibod
y (MF1), the epitope for which is located between residues 190 and 197, had
a high level of activity when cells (2060) harboring a gp46 with proline a
t position 192 were used and had no activity toward cells (1010) with a ser
ine at this position. Therefore our results establish that certain amino ac
id substitutions of gp46 may drastically affect the antigenicity of the mol
ecule and the biological activity of the antibodies elicited.