- although infectious agents express hundreds to thousands of determinants ...
- they expose on the surface of infected cells only one or a few antigenic sites that are relevant for recognition by the host's T cell pool.
-
on the intact infectious agents, only one or few antigenic determinants
are exposed that are both important for virus infection and are accessible
to B cell receptors and protective antibodies. Eg in VSV
the only determinant exposed on the surface is the tip of the glycoprotein
to which the neutralizing antibody binds and because of size restrictions,
only one antibody can bind at a time. Other antibodies cannot bind determinants
that lie between the glycoproteins or inside the virus particle. Isolated
purified glycoprotein of VSV has several antigenic sites, including the
tp exposed on the intact virus particle. The other determinants can bind
antibodies that have been generated during a VSV infection against fragments
of the envelope and against released glucoprotein. These additional antibody
specificities can be measured experimentally in a binding assay. However,
only antibodies specific for the tip are protective. Thus, antibody responses
measured to isolated proteins measure polyspecific and polyclonal antibody
responses. In contrast, virus-neutralizing antibody responses are mono-
or oligo-specific and often oligoclonal. - similarly, although only one or few specific T cell epitopes are expressed by infectious agents in the context of one individual's MHC haplotype, basic immunological studies often examine T cell responses against multiple minor or major histocompatibility differences that represent hundreds to thousands of different T cell epitopes. Thus, polyspecificity and polyclonality of T or B cell responses may suggest specific responses that in fact reflect cross-reactivity.
or dengue virus
cannot protect against other strains. Therefore, although most specificities
of B and T cells induced are the same for all strains, only the neutralizing
(protective) antibodies define specificity of immunity. In contrast to
protective determinants on infectious agents or toxins, model antigens
often used in immunological research expose multiple (between 10 and 1000)
antigenic sites on particular proteins, or in mixed antigen preparations.
Similarly,
experimental animals raised under nonphysiologically clean conditions may
skew the specificity of reactivity due to reduced nonspecific, concomitant
immunity and unwanted bystander effects.
