The self/nonself issue: A confrontation between proteomes

Abstract

Antibodies are immunoglobulin proteins that interact with specific areas on the surface of antigen proteins. These areas are referred to as B-cell epitopes. Identifying B-cell epitopes in order to induce a specific antibody response constitutes the unresolved core of immunology. Practically, the identification of epitopes in proteins is the fundamental, preliminary step in designing effective immunotherapy for cancer and infectious diseases as well as autoimmune pathologies.1-3 As a logical consequence, recent decades have seen determined efforts aimed at identifying and defining antigen epitopes. To understand the molecular determinants characterizing epitopic structures, immunology has used the self/nonself concept. [4][5][6] For decades, immunologists have based their studies, reasoning, experiments and clinical treatments on the idea that the immune system works by distinguishing between self and nonself.4,5 However, theoretical and experimental considerations lead to the recognition that there are no known molecular mechanisms that can explain how peptides of self-origin can be discriminated qualitatively from peptides of nonself-origin. 6 So, for example, how can the hexapeptide VLDVGG, which occurs in two different human proteins, be discriminated from the hexapeptide VLDVGG, which occurs in 380 bacterial, viral, protozoan and other organism proteins? How can the heptapeptide PPPPPPP, which occurs in 625 human proteins, be catalogued as self or nonself and distinguished from the heptapeptide PPPPPPP, which occurs in 12,883 bacterial, viral, protozoan and other organism proteins?

Selfness-nonselfness in designing an anti-B19 erythrovirus vaccine

“…22 The similarity profile was determined using viral pentapeptides. Pentapeptides represent the minimal functional unit in immunobiology, [23][24][25][26][27][28] and are thus an appropriate basis for assessing functional-structuralimmunological analyses. The B19 erythrovirus-versus-human pentapeptide profile is illustrated in Figure 1.…”

“…Five amino acids is the minimum unit able to evoke humoral and cellular immune responses and to stimulate immune recognition. [23][24][25][26][27][28] Thus, the similarity profile illustrated in Figure 1 is a measure of the potential immunological cross-reactivity platform existing between B19 and the human host. Quantitatively, Figures 1 and 2 indicate that an anti-B19 erythrovirus vaccine containing B19 proteins would carry a cross-reactivity potential quantifiable in hundreds of hits spread across the human proteome.…”

“…The A pentapeptide similarity analysis of the B19 viral proteins was conducted against the human proteome as described under Methods (see also refs. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Briefly, the number of matches scores the similarity level to the human proteome for each pentapeptide, and is obtained using pIR perfect peptide Match program (http://pir.georgetown.edu).…”

Searching for an effective, safe and universal anti-HIV vaccine: Finding the answer in just one short peptide

“…As advocated by Kanduc,[32][33][34][35][36][37] only vaccines based on unique antigenic peptides might guarantee no/low cross-reactivity and the highest specificity. Hence, as a first step in this study, we searched for pentapeptides unique to the viral proteins.…”

“…In any case, and most importantly, the eventual vaccine preparations would be safe. Being based on peptide sequences not present in the human proteome, these vaccines will probably be free of cross-reactivity, [32][33][34][35][36][37] therefore nullifying the risk of autoimmune collateral events, even following repeated administration. In conclusion, global and safe protection from HIV infection appears to be at hand.…”