Minor antigenic determinants

Does not identify those patients who react to a minor antigenic determinant (i.e., anaphylaxis) does not reliably predict the occurrence of late reactions patients with a negative skin test may still have allergic reactions to therapeutic penicillin... 

In addition to the penicilloyl determinant several other antigenic determinants are involved in penicillin allergy, the so-called minor antigenic determinants. Although much work has been carried out to establish the chemical structure of these determinants and the pathways to their formation (as reviewed by Schwartz 1969 Dewdney 1977) no firm conclusions have been reached as yet. 

Benzylpenicilloic acid is the main hydrolysis product of benzylpenicillin and is able to elicit wheal and flare reactions when used in skin tests in some patients allergic to penicillins. It has therefore been considered as one of the minor antigenic determinants of penicillin allergy (Siegel and Levine 1964 Voss et al. 1966) although the precise chemical nature of the determinant(s) derived from penicilloic acid has not been elucidated. The proportion of patients responding in skin test to penicilloic acid varies between 21% and 55% (Table 1). 

The degree of specificity of the MAB may also present other disadvantages in assay development for some antigens. For instance, MABs to viral strains may be so specific that they do not cross-react with other minor strains of the same virus. The mixed response of polyclonal antibodies is likely to be directed to several antigenic determinants, one or more being present on each strain. 

FIGURE 16.10 Hapten determinants formed by penicillins that contain a p-lactam ring linked to various side chains (R). The primary route of haptenation involves acylation of the E-amino group of lysine residues of serum or cell surface proteins to form a penicilloyl or major antigenic determinant. Isomerization of penicillin leads to the generation of compounds that form disulfide bonds wdth the cysteine sulfhydryl groups of proteins. These epitopes are termed minor determinants. 

Fig. 4 a, b. Formation of penicilloyl, penicillenate, and other minor determinants from penicillin, a Routes to the formation of the penicilloyl determinant and its further degradation products, b Possible pathways to the formation of the benzylpenicillenate antigenic determinant... 

There is no evidence for a common evolutionary origin of J chain and the immunoglobulins. Their peptide maps, antigenic determinants, and partial sequences have shown no similarities (105,181). A minor resemblance to H chains is the presence in J chains of a blocked N-ter-minus (pyrrolldonecarboxylic acid) (193). 

AntipeniciUin antibodies are detectable in virtually aU patients who have received the drug (and in many who deny previous exposure). Immediate allergic reactions are mediated by skin-sensitizing or IgE antibodies, usually of minor-determinant specificities. Accelerated and late urticarial reactions usually are mediated by major-determinant-specific skin-sensitizing antibodies. Some reactions may be due to toxic antigen-antibody complexes of major-determinant-specific IgM antibodies. 

In a cell there are a lot more protein species than RNA species (i.e., a protein chip would have to have many more spots than a DNA chip). Is that doable Theoretically, sure. You would just have to covalently stick a corresponding number of monoclonal antibodies to the chips—a minor task with a few hundred thousand highly specific, highly afhne monoclonal antibody species. Real life has even more trouble in store. Although it may be possible to bind the countless antigens to the countless antibodies on the chip, how would you determine the binding ... 

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