Background T cells recognize a complex between a specific major histocompatibility complex (MHC) molecule and a particular pathogen-derived epitope. vaccine or diagnostic with ethnically biased populace protection could result. Results To address this issue, an algorithm was developed to calculate, on the basis of HLA genotypic frequencies, the portion of individuals expected to respond to a given epitope set, diagnostic or vaccine. The population protection estimates are based on MHC binding and/or T cell restriction data, even though tool can be utilized in a more general fashion. The algorithm was implemented as a web-application available at http://epitope.liai.org:8080/tools/population. Conclusion We have developed a web-based tool to predict populace protection of T-cell epitope-based diagnostics and vaccines based on MHC binding and/or T cell restriction data. Accordingly, epitope-based vaccines or diagnostics can be designed to maximize populace protection, while minimizing complexity (that is, the number of different epitopes included in the diagnostic or vaccine), and also minimizing the variability of protection obtained or projected in different ethnic groups. Background T lymphocytes identify a complex between a specific major histocompatibility complex (MHC) molecule and a particular pathogen-derived epitope. Thus, a given epitope will elicit a response only in individuals that express an MHC molecule capable of binding that particular epitope, explaining to a large extent the phenomenon known as “MHC restriction” [1]. In humans, MHC molecules are known as human leukocyte antigen (HLA) molecules and two different types exist: class I and class II. HLA class I molecules mostly bind peptides derived from the endogenous processing pathway, and their acknowledgement is primarily associated with cytotoxic T lymphocytes (CTL), which are most Duloxetine enzyme inhibitor important for antiviral and anticancer immunity responses. By contrast, HLA class II molecules bind peptides typically derived from the extracellular milieu, and they are important for helper T lymphocyte (HTL) responses, which regulate antibody and cytotoxic responses. HLA molecules are extremely polymorphic. Over a thousand different HLA allelic variants have been defined to date [2]. Specific HLA alleles are expressed at dramatically different frequencies in different ethnicities [3,4]. Therefore, in the design and Duloxetine enzyme inhibitor development of T-cell epitope-based diagnostics or vaccines, selecting multiple epitopes with different HLA binding specificities will afford increased protection of the patient population. A relevant goal, in this context, might be to identify optimal units of HLA alleles with maximal coverages for different populations [5,6]. Considerable analyses by Longmate and coworkers [7] suggested that 90% populace protection of several ethnic groups can be achieved by targeting eleven different HLA molecules. However, 90% protection of African and Asian ethnicities required four or more additional molecules. Dawson et al. also analyzed the problem [8] and concluded that to reach 80% protection, 3 to 5 5 HLA molecules were required in a given ethnicity, but the actual HLA specificities required were different in different ethnic groups. An important consideration in the process of epitope selection for any T-cell epitope-based diagnostic or vaccine is usually that the patient population protection afforded by a given epitope set does not simply correspond to the sum of the protection of the individual components. To Duloxetine enzyme inhibitor determine the protection afforded by a given set of epitopes with multiple and/or overlapped HLA binding specificities, a more comprehensive approach, taking into account MHC binding and T cell Rabbit polyclonal to ADORA1 acknowledgement patterns, is required for this purpose. A suitable algorithm was previously utilized [9-11] but not described in detail. This method calculates the portion of individuals predicted to respond to a given epitope or epitope set on the basis of HLA genotypic frequencies and on the basis of MHC binding and/or T cell restriction data. In this paper, we describe the algorithm and its implementation as a web application available to the public. We believe this is a useful tool to Duloxetine enzyme inhibitor aid in the design and development of T-cell epitope-based diagnostics and vaccines intended to be effective across diverse populations. Implementation For a given HLA gene locus, let is an indication function. For calculation of protection by epitope units restricted to MHC alleles of multiple is an indication function, and where Duloxetine enzyme inhibitor em n /em is the total number of epitopes and em k /em is the quantity of epitopes in a subset. For example, for a set of 20 epitopes, there will be a total of 1 1,048,575 combinations of epitope subsets that needs to be evaluated. Therefore, a strategic searching approach must be devised to computationally accomplish this task. In summary, with the help.